The Health Affairs Blog homes in on the drug pricing regulatory system in Germany, known as the Act to Reorganize Pharmaceuticals Market in the Statutory Health Insurance System (AMNOG).
Much like the U.S. in relation to Europe, Germany once stood out with drug prices averaging 26 percent higher than the EU average. Thanks to the AMNOG process, Germany saved over $1 billion in new drug spending in 2015; the average drug discount came out to be 21 percent.
This article provides a detailed walk-through of the Institute of Quality and Efficiency in Healthcare’s (IQWiG) drug review process to determine the benefits of a drug once it’s been launched on the market. In brief, should a drug add major benefits, considerable benefits, or some moderate improvement against the standards-of-care on the market, the manufacturer and the insurance provider organization in Germany enter into negotiations over pricing. Should a drug not add quantifiable benefits, fewer or no benefits over current therapies, the drugs are priced in accordance with existing treatments. Should a company choose to sell one of these lower-ranked drugs at a higher price, the patient is responsible for covering the difference. A company is required to reimburse excess revenues to payers for any drug that had a high price tag prior to an unfavorable IQWiG review.
It’s generally difficult to compare the fragmented payer system in the U.S. to the single payer systems in countries like Canada and the U.K. However, Germany also has a multi-payer system. Similarly, the U.S. is currently venturing down the path toward value-based payment programs for new drugs, and the IQWiG is essentially making a decision on how a drug should be priced based on its value.
When thinking about complex problems, like drug pricing, it’s simplistic to outright say, “Yes, this is how the U.S. should manage the cost of high drug prices.” That said, however, I’m a big proponent of looking at how other countries have succeeded in regulating drug prices. This article makes some interesting points and is certainly worth a read. Though we don’t know yet what the new U.S. administration is going to be focusing on in regards to drug pricing, it wouldn’t surprise me if the U.S. does end up with an IQWiG-like organization in the future.
In the midst of the holiday season, the FDA sneaked the finalized version of its guidance, Clinical Pharmacology Data to Support a Demonstration of Biosimilarity To a Reference Product, into the world. One big contention with the draft guidance, released in 2014, was the terminology used to define the FDA’s assessments of a biosimilar’s analytical similarity (during development). As BioPharma-Reporter describes, the FDA originally labeled the different categories of similarity as “not similar; similar; highly similar; and highly similar with fingerprint-like similarity.”
I dare say, even those who are not currently working to approve a biosimilar could certainly see why these non-descript terms wouldn’t cut it. The FDA’s revision does a little bit better defining the different types of similarities. The revised terms are: “Insufficient analytical similarity; analytical similarity with residual uncertainty; tentative analytical similarity; and fingerprint-like analytical similarity.”
I was a little disappointed to see the term fingerprint-like similarity revisited. It had been quite some time since I’d heard the FDA refer to a highly similar biosimilar as one that had “fingerprint-like” similarity. Indeed, even some of the conversations I had with members of the industry suggested the FDA was taking a step back from using this term given the fact a biosimilar (and biologics in general) cannot be that similar to each other. My main concern about the phrase “fingerprint-like similarity” is that it will end up being used only to describe biosimilars that, perhaps, jump through more hoops for an interchangeability designation. This, in turn, would establish an incorrect hierarchy of quality between interchangeable and non-interchangeable (but approved) biosimilars.
Given South Korea’s trailblazer status in biosimilar manufacturing, I was interested to learn more about biosimilar uptake in the country. After reviewing claims data from April 2009 to March 2014, authors of a report published in Arthritis & Rheumatology determined biosimilar infliximab uptake increased by 19 percent between November 2012 (when the product was launched) and March 2014. Overall, one-fifth of all infliximab claims in South Korea were for the biosimilar version. As can be expected in any market, not just in South Korea, an anti-TNF biosimilar on the market can cause decreases in demand for the different TNF innovators. For instance:
Before November 2012, each month there were 33 more infliximab claims, 44 more etanercept claims, and 50 more adalimumab claims…. After November 2012, there were significant changes in the slopes for trend in usage, with additional increases in the use of branded and biosimilar infliximab (9 more claims per month) and decreases in the use of etanercept (−52 claims per month) and adalimumab (−21 claims per month).
FiercePharma wrote a great summary of the pending U.S. biosimilar launches and challenges in the U.S., as well as the ongoing market dynamics in the EU moving into 2017.
2017 is looking to be a big roll-out year for biosimilars in the U.S. Late in November, Pfizer launched Inflectra at a 15 percent discount. However, analysts from Sanford Bernstein expect Inflectra uptake will be slow for the first half of 2017, only accelerating in the later part of the year. The U.S. also faces pending legal decisions and a new presidential administration, which could slow uptake. I’ve heard 2016 referred to as the year of biosimilar approvals. 2017 will likely be the year we see more approvals and, hopefully, see some of these approvals result in product releases.
The EU, on the other hand, is expected to have its best biosimilar year yet. As Sanford Bernstein’s Ronny Gal predicted, 2017 will be a “watershed year for biosimilars.” Merck’s Remicade experienced a loss of 26 percent in the most recent quarter because of competition from Celltrion. Remsima has been pegged to conquer half of the European market by the end of 2017. And, when it comes to Amgen’s Enbrel, Bernstein analysts predict the biosimilar will snare a third of the market.
I’ve been paying close attention to the blogs being published by the Center for Biosimilars. One recent blog about how indication-specific pricing could be used for biosimilars. Stan Mehr writes:
One type of alternative reimbursement model that has been the subject of a bit less press is the indication-specific pricing (ISP) contract. Under ISP, the payer and pharmaceutical partner sets different levels of pricing for each indication or for patient subpopulations eligible for treatment…. Why should the health system pay the same price, on a per-dose basis, for a drug that is only 40 percent effective in treating psoriasis versus 75 percent effective in relieving the symptoms of psoriatic arthritis?
I’ve always been interested in the concept of indication-specific pricing as a way to lower health care costs. But I have concerns about Mehr’s discussion on applying the concept to biosimilars — at least this early in the biosimilar game when education of physicians is key. He writes:
What if, to help clinicians gain comfort with the biosimilar and increase rapid uptake, the indication for which the medication was clinically tested was priced at a lower level than for other indications?
As an industry, we’re already struggling to help physicians understand the concept of extrapolation. Lowering the biosimilar price for the indications only tested in human trials would continue to emphasize the importance of clinical trials rather than analytics and totality of evidence. It would also suggest the biosimilar is more effective in those conditions, solely because it went through clinical trials. For now, I’d argue it’s more important to have one lower price for the extrapolated biosimilar, if only so physicians can learn how to evaluate biosimilars (compared to biologics) and trust extrapolation.
Having read and written many times about the work regulators are doing to encourage streamlined biosimilar development, I was happy to hear of the EMA’s newest program. In February, the agency plans to launch its new biosimilar scientific advice pilot project, which will help companies determine what studies they should conduct after they have their quality, analytical, and functional data. As this is just a pilot program, the agency will only be accepting six scientific advice requests to start off. Overall, this program will give companies an opportunity to ask questions targeting quality development and non-clinical and clinical development. Though biosimilar makers already have the opportunity to approach the EMA for this kind of scientific advice, the current program does not include a review of existing data from the development program.
Stan Mehr, in a blog on the Center for Biosimilars site, discusses the controversial impact couponing can have on healthcare costs in general, as well as the specific threat they may pose to biosimilars. According to an article Mehr cites from the New England Journal of Medicine, couponing has encouraged a 60+ percent increase in brand prescriptions. Mehr summarizes the article’s findings:
For the nation as a whole, every copayment coupon adds up to $120 million over the first 5 years after a generic drug is introduced. For the manufacturers of 85 medications that first faced generic competition between 2007 and 2010, couponing boosted spending anywhere from $700 million to $2.7 billion over a scenario in which couponing did not exist.
Depending on the price of the biosimilar co-pay (which ultimately depends on which tier biosimilars are assigned to on the formulary), a coupon could help lower the price of the biologic below that of the biosimilar. Mehr’s article delves into several ways payers can address couponing programs in order to ensure biosimilars remain relevant. But the point that caught my eye was his argument that couponing could be a tool biosimilar makers turn to, as well, to even the playing field between its biosimilar and the biologic. As he writes:
In the case of biosimilars versus originator medications, drug coupons offered by the manufacturer of Enbrel, for example, actually make it less expensive for the patient to purchase the originator than the biosimilar, assuming a lower-copay biosimilar tier. That is, unless Sandoz, the maker of the approved etanercept biosimilar, matches Amgen’s couponing program. In that case, there would be incentive or disincentive for either product, from the patient’s perspective.
We’re already seeing this happening from Sandoz, which launched its One Source copay program earlier this year. Through the program, patients’ copays for Zarxio are covered, limiting the amount the patient needs to spend to $10 each month. I expect we’ll be seeing more of this, at least as companies begin releasing the first biosimilar for each reference product in order to better compete with the brand. (But the question that remains for me, and I’m assuming others, is how applying these co-pay programs — which tend to be controversial — to generics will impact general perception of them.)
There was also an interesting article in FiercePharma that highlighted some of the additional marketing challenges biosimilars will encounter. For instance, while innovators have the money to launch direct-to-consumer advertising, many biosimilar companies won’t have that kind of money starting out to draw patients. Not to mention, because biosimilars need to be cheaper than innovators, advertising would only add to the drug’s cost and cut their margins short. Many of the bigger companies, like Pfizer and Novartis, have decided to tap large sales forces to spread the word and educate physicians and patients.
The Supreme Court has turned down ruling on whether a biosimilar maker should be required to have a 180-day wait after FDA approval. Apotex was also hoping to get the Supreme Court’s views on whether a company that voluntarily follows the patent dance should be required to wait six months to launch. This is obviously a blow for Apotex, which was successful in knocking down some of Amgen’s patent protection for filgrastim and pegfilgrastim in September.
However, this is still hope for the biosimilar industry to see changes to the 180-day requirement. Just last week, the solicitor general passed Sandoz vs. Amgen on to the Supreme Court for its deliberation. (Important to note: Apotex did not have the solicitor general’s recommendation on its side, unlike Sandoz. This fact makes me optimistic for a better outcome for Sandoz vs. Amgen.) The Supreme Court would be ruling on whether the 180-day notice is required to come after the FDA approval, or if it can occur before. There had been some chatter that Amgen vs. Sandoz could also include Apotex’s arguments as well, however this was not a recommendation from the solicitor general.
Though pharma was breathing a sigh of relief following the election results, Hillary Clinton’s hopes for more drug pricing control might end up coming true after all. News on Twitter today reveals a new bill proposal was filed by Representative Rosa DeLaura of Connecticut calling for the FDA to establish a review board to regulate drug and device prices. While Clinton was calling for a group of federal officials to review price hikes for drugs and determine if they are justified or not, this bill calls for a new unit focused on pricing within the FDA.
Interestingly, a former FDA employee included a similar proposal in his STAT article “7 Ways To Make The FDA Great Again, From A Former Agency Official.” He argued in favor of the FDA creating a similar entity to that of the U.K.’s price watchdog, National Institute for Health and Care Excellence (NICE). This is something we could definitely learn from the FDA’s European counterpart, the European Medicines Agency (EMA), he writes.
Despite the fact Australia’s regulatory agency ruled biosimilars can be swapped at the pharmacy level, uptake has been particularly slow in the country. I never have to look very hard to find out why that’s the case. Australian pharmacists tend to be particularly vocal about the differences between biosimilars and biologics and the importance of caution. Take for instance, this article published in the Australian Prescriber. The article emphasizes the need for pharmacovigilance because of concerns over immunogenicity. These concerns are certainly not restricted to Australia. But I found this trend of Australian pharmacists writing about biosimilars particularly interesting, given the fact that I have yet to read any articles from pharmacists in the U.S., or the EU for that matter.
Australia’s Department of Health has launched a new Biosimilar Awareness Initiative. PharmaDispatch reports this was a joint effort between the government and the Generic and Biosimilar Medicines Association. So far, the initiative launched a public website targeting consumers and healthcare professionals. In the upcoming months, there are also plans to launch brochures prior to the PBS-listing of Brenzys (etanercept).
Drug Discovery & Development put together a short list of the challenges biosimilar companies face commercializing their biosimilars. Education and pricing strategies are a big challenge. But the one that caught my eye was the need for alternative promotional tactics. In fact, I think the language used to describe the selling model does a particularly nice job of demonstrating the amount of juggling biosimilar companies have to do to get their product to market. Branded drugs gain their market shares by promoting their clinical profile. Since a biosimilar has the same clinical profile, that makes it more difficult to promote. DDD writes:
The selling model for biosimilars needs to adapt. Biosimilar manufacturers need to educate prescribers using a ‘bottom-up’ selling approach to ensure they understand the clinical benefits of the biosimilar product upon launch. However, a ‘top-down’ selling approach is also needed to truly drive adoption. Manufacturers should focus promotional tactics on payers and hospital budget holders to ensure they understand the potential cost-savings associated with biosimilars so they are placed on preferred tiers and hospital formularies.
Health Canada has made several changes to its biosimilar submission requirements, including a change in terminology and clarifications to the scientific basis for biosimilar authorization, criteria for reference products, clinical and non-clinical data requirements, authorization of indications, and labeling requirements. The most interesting changes include Health Canada’s decision to eliminate the term extrapolation and replace it with authorization of indications. This move was to eliminate any confusion that clinical data is extrapolated from one indication to another. Similarly, Health Canada also expects the manufacturer to include a summary of the comparative data in the product’s monograph. The biosimilar’s monograph may also now include safety and efficacy info from the originator’s label.
I’d urge you to take a peek at this nice summary of the changes on JDSupra for all the details. At the DIA biosimilars 2016 conference, Health Canada gave a regulatory update, which I plan to produce into a feature article over the next week. Some of these topics will be covered and will, perhaps, provide more context for these changes. Stay posted!
A forecast from QuintilesIMS predicts total spending on medicines will reach $1.5 trillion by 2021. This will be a 33 percent increase from the total spent in 2016. Overall, however, this growth, which will occur at a 4 to 7 percent compound annual growth rate (CAGR), will be less than the 9 percent growth seen between 2014 and 2015. The U.S. in particular will see 6 to 9 percent growth, down from 12 percent in 2015. Patent expiries and the entrance of biosimilars will play a key role in the decline of spending.
In an online editorial in JAMA, Deborah Schrag and Harold Burstein, both of whom work at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, came out in support of Mylan and Biocon’s trastuzumab biosimilar. The biosimilar (plus docetaxel or paclitaxel), which was investigated in the Heritage Study, was found equivalent to Herceptin (plus chemo) in 458 women with ERBB2-positive metastatic breast cancer.
I was particularly impressed with the confidence these authors demonstrated in the biosimilar. Take for instance, this:
In answer to the proverbial question “Would you use the trastuzumab biosimilar for your mother if she had ERBB2-positive breast cancer?” the answer should be yes.
I was thrilled to see this sentence appear in JAMA, of all places. Recent scholarship exploring physicians’ views on biosimilars reveals that doctors trust peer-reviewed journals for their information even more than the FDA. Peers also made the list of physicians’ most trusted resources, so it’s great to see a clinician and clinical investigator come out in support of this trastuzumab biosimilar in breast cancer. (They encourage a "trust but verify approach" when extrapolating to gastric cancer, though they argue the data gleaned from the Heritage trial will also likely support extrapolation.)
In addition, both of these clinical investigators had a stern word on the ethics necessary for biosimilar trials in particular.
Unless the price of the trastuzumab biosimilar is set considerably lower than the 25 percent to 30 percent discounts typically seen during the last decade for biosimilars entering European markets, treatment will remain inaccessible for far too many patients. It is morally indefensible to foster a clinical trials system that recruits participants from low- and middle-resource countries primarily to benefit market competition in richer countries. The ethical conduct of biosimilar trials requires ensuring that the communities of trial participants should have realistic access to drugs they have helped to develop.
The National Law Review writes the Italian Chamber of Deputies has approved the Draft Budgetary Law of 2017, which forbids automatic substitution of biosimilars for an originator and introduces rules on designing public tenders for biologics and biosimilars. According to the Review, one of the most “novel” changes in the law was:
In public tenders for biosimilars, two products with different active substances may not be included in the same procurement lot even where they have the same therapeutic indications. [This] represents an important novelty. In fact, an Italian administrative court has recently found that it is legitimate to include two originator biologics with equivalent therapeutic indications in the same procurement lot.
The country is currently at work on a Concept Paper on Biosimilars, which is expected to be published by the Italian Medicines Agency (AIFA). The AIFA completed public consultation on the paper last summer. This latest revision to the law is expected to shape the Concept Paper moving forward.
There was a great article in the latest issue of AISHealth about the future of the Biologics Price Competition and Innovation Act (BPCIA) should Trump enact his plans to repeal the Affordable Care Act (ACA). Obviously, as the BPCIA legislation was part of the ACA, a repeal of the entire act could eliminate the biosimilar pathway, as well. This isn’t a situation biosimilar makers are treating lightly. As Bert Liang, CEO of Pfenex, told AISHealth, Pfenex has queried to determine how BPCIA might be affected by changes to ACA. However, he remains optimistic overall that BPCIA isn't likely in danger.
Similarly, an anonymous industry member predicted the BPCIA would continue to survive should the ACA disappear:
I would expect BPCIA to be re-enacted. [It offers the] best and most immediate way to mitigate prices in the specialty space.
This is likely an accurate prediction, given the importance of biosimilars for companies and the loudly protested health care costs that were a big talking point during the election.
According to Business Korea, South Korean biotech and healthcare companies are extending their businesses into Japan. Though the article doesn’t mention any biosimilar companies currently entering Japan, this movement is certainly worth being aware of, given Korea’s increasing role in the biosimilar space.
Japan was also the subject of BIO’s censure more recently after the Japanese government cut cancer-drug Opdivo’s price in half. According The Pharma Letter, this move poses a risk for innovators in the nation which BIO had previously praised as being friendly to biotech R&D and innovation. This willingness to drastically lower innovator prices would certainly set up a competitive atmosphere for biosimilars. But the question then becomes will the low prices out of the gate serve as a disincentive to biosimilar makers and just keep the brands in the lead?
There are rumors circulating that Novartis is eyeing an Amneal acquisition in order to bolster its generics unit, Sandoz. Between generics pricing pressures and an increase in the FDA’s rate of generics approvals, the space is fraught with competitive pressure. According to FiercePharma, many of the big generics players — Mylan, Teva, and Sandoz — have been troubled by the smaller margins that come from reduced prices. We’ve already seen Mylan and Teva become even bigger generics powerhouses through recent acquisitions, and Sandoz’s similar move toward a potential Amneal deal suggests serious players — including mid-size companies — could face future consolidation pressures.
On the surface level, this deal could serve as a boon to biosimilar-maker Sandoz, which would gain more manufacturing capacity, especially in the injectables space. But talk of mergers and growth of super powers within the generics space always gets me thinking about the growing biosimilar space. There’s already a wide array of large and small companies looking to bring biosimilars market, but pricing concerns loom. (It’s also hard to know yet how many players the market will feasibly hold.) Discounts these days are not yet steep, but as more players hit the market, discounts are forecast to reach upwards of 70 percent. I can’t help but wonder if the biosimilars space will find itself facing the same consolidation pressures. If it does, we’d most likely be looking at a market dominated by a few big brand and generics players.
Comparator sourcing has regularly been called out as one of the biggest issues facing biosimilar makers. Not only is it difficult to attain the necessary quantity of the comparator from a number of different lots, but Risk Evaluation and Mitigations Strategies (REMS) are now becoming competitive weapons. Many drugmakers hide behind REMS in order to avoid handing out lots of their drug to biosimilar and generics makers. But there was an interesting article in the Business Standard on turning to emerging markets for comparator drugs. According to this article, there has been a rising demand for comparators in India as biosimilar development becomes more prominent within the nation. But 95 percent of comparators are sourced in the U.S. or EU, partially because of import procedures which favor foreign suppliers outside of India. There are a number of benefits to going to emerging markets in order to find comparators, including the lack of a well-developed health insurance infrastructure. This infrastructure helps lower the overall cost of the innovator drug, and emerging markets generally offer larger quantities/numbers of batches for the required testing. This article is certainly worth a read, given the concerns I've heard voiced on this topic over the past year.
At the AAPS meeting in Colorado this week, Pfizer and the FDA emphasized the challenges facing drugmakers using Fast track, Breakthrough, Priority, and Accelerated designations to get their drugs more quickly to market. These designations offer drugmakers more flexibility in their clinical development, as well as in the regulatory review. However, this abbreviated development poses a challenge for Chemistry, Manufacturing, and Controls (CMC) strategy. Because a drug could face an earlier approval via these pathways, companies have to invest in infrastructure quite early—a big risk given there's always a chance the drug won’t end up receiving approval. An expert from Pfizer was quoted in an in-Pharma Technologist article, saying:
Sponsors may have to make at-risk investment as commercial manufacturing programs have to be ready to go. The CMC part of the process is by far the most expensive so therefore, there is a need for a company to have important discussions about triggering an at-risk investment.
The four abbreviated pathway options mentioned above are not applicable to biosimilars. But biosimilar sponsors already face an abbreviated clinical development schedule. This article peaked my interest because I’m already hearing talk about abbreviating the biosimilar clinical pathway even more to rely only on PK/PD and immunogenicity studies. Obviously, biosimilar makers are already accustomed to abbreviated development, and CMC is the lifeblood of biosimilar development. But should development continue to evolve and become more sophisticated over time, these infrastructure and CMC challenges could certainly apply to biosimilar makers, as well.
Following Donald Trump’s election as president of the U.S., I’ve read a number of articles speculating about how presidency will impact the pharma industry. So far, from a general market perspective, pharma stocks have shot up, likely because Trump didn’t focus as extremely on drug prices as Hillary Clinton. Similarly, his corporate tax policy is expected to encourage more mergers within the healthcare space, and will likely serve as a boon to the big players in the pharma industry. But overall, there are two topics outside of drug pricing many in the pharma industry are waiting to hear about (including myself). The areas in question are Intellectual Property (IP) and what will come of biosimilars following a possible repeal of Obamacare.
Obviously, a complete repeal of Obamacare would eliminate the pathway for biosimilar approval, as it was created within the Affordable Care Act (ACA). That said, most reports seem to suggest Trump is currently leaning toward revising the ACA legislation, rather than eliminating it altogether. Similarly, given the cries for lower drug prices and the importance of biosimilars for drugmakers, I’d find it hard to believe the pathway would be eliminated just like that. The same goes for the Biologics Blog, which argues:
It seems unlikely that the recently-enacted BPCIA, both the regulatory pathway and its litigation framework, will come to an end under Trump.
Now, one of the areas we could very well see impacted is the timeline of the Solicitor General in determining whether to relegate the Amgen v. Sandoz cross-petitions to the Supreme Court. As the Biologics Blog states, the Solicitor General may choose to weigh in after Trump’s executive team is in place and he has officially taken office. Who Trump appoints to the Supreme Court could impact any decisions of the Supreme Court, should the Solicitor General pass Amgen v. Sandoz on.
That said, innovators in biopharma might be somewhat nervous considering Trump’s plans to abolish the Trans-Pacific Partnership (TPP). As The Wall Street Journal reports, members of Congress have announced they will not be moving forward with the TPP following the recent election, and the Obama administration has admitted defeat. One of the most contentious issues was IP protection for biologics. The final proposal gave countries the option of anywhere from five to eight years of exclusivity. (Though if a country selected five years exclusivity, there were “other methods” of protection for those drugs.) This was the closest to standardizing patent protection among the TPP nations — some of which didn’t even have a period of exclusivity to begin with. This could bode well and present fewer IP barriers for biosimilar makers targeting the emerging markets included in the TPP. But for innovators, this development will leave a lot of questions open about how Trump will approach future IP issues.
Finally, one of the most compelling, and, frankly, upsetting articles I’ve read about the fate of biosimilars appeared in Business Korea. A big concern is that small and medium-sized companies in Korea will have a more difficulty entering the U.S. market because of Trump’s crack-down on freer trade. According to one scholar at a Korean university:
‘Since Trump is a protectionist and will pursue U.S.-centered policies in the intellectual property sector which will be disadvantageous to the Korean pharmaceutical industry with strong competitiveness in generic drugs.’
One of the biggest concerns I’ve had, which was voiced in this particular article, was that “Trump Care” is more likely to favor the innovator companies, such as AbbVie, Merck, Amgen, and Gilead. And the scary part:
For this reason, Korean companies are urged to hurry to develop high quality new drugs rather than generic drugs. ‘It will take a long time and will not be easy, but, ultimately, new drug development is an alternative,’ said a representative of the Korean bio industry.
Given Korea’s influential and leading role in the biosimilar space so far, this statement should not be taken lightly.
When I travel to shows, I always end up walking away with information from presentations I unfortunately can’t fit into a full article right away. I garnered one of these bite-sized tidbits back in September at the GPhA biosimilars show. In her keynote address, the FDA’s Director of CDER Janet Woodcock discussed the importance of continuous manufacturing for the generic industry. Woodcock observed that continuous manufacturing is currently drawing a number of innovators, likely because of the high initial investment required. But this isn’t to say continuous manufacturing won’t play a huge role in the biosimilar space in the future. She stated:
It may well be the case the innovator side is first in this arena, because the biosimilar industry is focused on getting some products developed and getting them to market to prove this is a valid pathway for development. … But advanced bioprocessing is beginning to take off, and I think it will be something [the biosimilar industry] will help drive because it’s important to have affordable manufacturing so there can also be affordable pricing.
The rejection of Coherus’ Inter-Partes Review (IPR) against a Humira formulation patent is certainly a blow to Humira biosimilar makers. But it’s worth reiterating the IPR isn’t the end of the battle, nor does it close the book on this particular challenge. Though Coherus might not benefit from the abbreviated legal process the IPR offers, the company could still see success through the district court. In fact, as Coherus CEO Denny Lanfear discussed in a statement:
There are additional scientific and legal approaches available to address the various formulation intellectual property challenges, and all of the arguments raised in our IPR petition remain available in a District Court proceeding.
Similarly, this blow won’t necessarily predict the success another company could have against Humira. As one analyst told Biopharma-Reporter:
Biosimilars do not necessarily need to have the same formulation as the reference product. … The IPR on [the ‘166 patent] may not be important for all potential Humira biosimilar filers because they may have different formulations, and it’s unclear whether they infringe.
So, if you’re not quite sure how to feel about this loss, frustration over AbbVie’s solid IP maze is certainly warranted. (And, just as an FYI, AbbVie is in line to score yet another indication in the EU, this time for adolescents with Hidradenitis Suppurativa.) But I wouldn’t give up hope yet that someone (perhaps even Coherus) could still wheedle its way through that maze.
Based on the FDA’s final rule on how the FDA will handle citizen petitions, it would seem generic and biosimilar makers won’t find these petitions gumming up the release of their drugs. The biosimilar space in particular has received several of these petitions from AbbVie over the past year on interchangeability and labeling, none of which have been successful to date. Many of these petitions rarely raise valid scientific or legal concerns, yet can cause hold-ups in the approval of the drug. (A successful petition will somehow prove that a market delay is necessary to allay a threat to public health.) According to Regulatory Affairs Professionals Society (RAPS), PhRMA submitted several key changes, though FDA has since rejected them. One of PhRMA’s regulation suggestions included clarifying the FDA may take longer than the set 150-day review period for a petition. FDA argues, however, this is not feasible because it’s hard to predict how long it will take for an issue to resolve.
So far, the FDA has turned down the petitions that could impact biosimilars. But I wouldn’t necessarily expect this new rule will keep innovators from trying their hand with petitions. After all, the biosimilar industry is still in that interesting phase where policies are still being solidified and where labeling, naming, and interchangeability practices could easily be skewed as “a threat to public health.”
It’s a natural part of the biologic drug lifecycle to make changes in manufacturing processes. This was a huge topic discussed throughout DIA last week. And just in time, WHO has released its guideline on such changes for biologics and biosimilars. RAPS reports the key elements of this guideline:
The guideline calls on companies to decide whether they need to submit a supplemental application to regulators for each change to an approved biologic based on the results of pre- and post-change analytical testing. In addition to changes with a major or moderate impact, ‘all changes, regardless of the impact on quality, safety, and efficacy, should be recorded and retained by the manufacturer or [marketing authorization] holder.’ The draft also noted: ‘In general, no change should be implemented without the approval of the NRA [national regulatory agency] unless exempted in these guidelines (i.e. minor quality changes or quality changes with no impact).’
In the news recently was speculation that Merck KGaA is considering selling off its biosimilar unit. According to BioPharma-Reporter, the business was priced at roughly $1 billion, though this value was not verified by the company. For those of you interested in companies’ pipelines, thanks to BioPharma-Reporter, we can get a glimpse into Merck’s biosimilar business. Merck’s foremost candidate is its MSB11022, a Humira biosimilar, which is currently in a global Phase 3 trial. There is also MSB11202, which is rumored to be a rituximab biosimilar. Partnerships with Dr. Reddy’s for oncology biosimilars and Bionova (targeting the Brazilian market) are on the books. There has also been talk of an in-licensed, undisclosed late-stage autoimmune disease biosimilar candidate.
Biogen reported its Benepali and Flixabi biosimilars raked in $31 million in revenue, Market Realist reports. Benepali is currently available in 13 European markets, while Flixabi is available in Germany, the Netherlands, and the U.K. Market Realist provided a nice tidbit of information on Benepali in particular:
According to Biogen’s 3Q16 earnings conference, ~86 percent of nurses have preferred Benepali’s auto-injector device over Enbrel’s. This highlights the fact that Benepali has managed to compete with Enbrel on aspects other than price.
This is good information to know as companies proceed into an uncertain pricing environment for biosimilars. I discussed in a previous blog post (How Diabetes Patients Are Responding To CVS Lantus Drop [10.13.16]) that patients are connected to the device. Indeed, it seems they recognize the treatment by the device. Apart from the patients, it’s good to keep healthcare professionals in mind too, especially as we approach the oncology biosimilar push.
India may be implementing a form of “data exclusivity, which could make the country a less welcome place for biosimilar developers. According to The Times Of India, the department of industrial policy and promotion is considering extending the current four-year period of data exclusivity to 10 years. This would essentially mean a drug would be considered a “new drug” for a period of 10 years from its date of approval.
A domestic company which plans to launch within this period of 10 years will need to apply to the central licensing authority for approval. Under the existing regime, after the four-year period from the date of the first approval of any drug, a patent holder monitors generic applications in all major states. The proposed change to 10-year will provide a sigh of relief to big pharma, as they will no longer need to worry about approvals by state licensing authorities (SLAs) for 10 years.
The country has witnessed upwards of 200-some formulations sent in for approval after the conclusion of the four years of exclusivity. This could serve as a big threat to small and medium size companies especially trying to enter the market. The companies in the biosimilar space we tend to hear the most about include Biocon, Intas, and Zydus, which are all large companies. Regardless, recent estimates expect the biosimilar industry to bring in $40 billion by 2030. Add in extra exclusivity for originators, and we’re likely to face some delays in reaching that total. This data exclusivity period could also be added onto the list of challenges facing companies in the biosimilar space in India, which were outlined more fully in this Business Standard article. Included in the list are high investment barriers for regulated markets and slow market expansions in emerging markets. (This piece is worth a read for player both in and outside of India exploring biosimilar development.)
The FDA is currently facing 700 job vacancies in its new drug division. But because pharma companies are able to offer more alluring compensation, the FDA is struggling to hire and retain staff. (Though the issue isn’t as simple as raising salaries to compete.) According to The Washington Post, the FDA succeeded in bringing on 1,000 new employees to help eliminate the generics application backlog, but the Center for Drug Evaluation and Research (CDER) has 711 open positions to fill. One expert from Center for Biologics Evaluation and Research (CBER) states:
‘We move rather slowly — like a snail might be a better analogy…A young person with a family can’t wait four months for us to get through some of the federal hiring process. So if they have something else that’s more . . . expedient, they will take that.’ [This expert’s] team has 96 vacancies out of a ceiling of 1,137 positions…
This serves as a deep dive into some of the hiring issues we’ve been hearing about particularly in the biosimilar space. This was an interesting, though disconcerting, article to read, especially after the release of BsUFA II a few weeks ago, which emphasized a plan to increase hiring.
Sandoz reported some impressive sales for its Zarxio biosimilar. Since its launch in the U.S. last year, Zarxio sales have exceeded $100 million. Overall, the company’s biosimilar portfolio rose more than 40 percent to $262 million in the quarter. According to PM Live, the company is expecting its four biosimilars will hit $1 billion in 2016, though the article was unclear specifically what these four biosimilars are (besides Zarxio and Omnitrope). The company is facing an EMA regulatory decision for rituximab, and was sent back to the drawing board in the U.S. for its pegfilgrastim biosimilar. (The latter is still up for review in the EU.) It’s not clear if this $1 billion tally includes Erelzi, which has yet to see the U.S. market post-approval because of legal hassles.
I’m getting a sense there’s a long way to go before there is widespread uptake of biosimilars in Ireland. According to The Irish Medical Times, the Department of Health is turning its attention to the biosimilar space in order to develop policies to improve uptake. As is the case everywhere, drug prices are starting to alarm the Irish Government. According to The Times, an agreement with the Irish Pharmaceutical Healthcare Association (IPHA) specifies a 30 percent reduction in the price of biologic medicines when a biosimilar medicine enters the market. Overall, the goal of this agreement is to garner savings from IPHA companies through 2020. Ireland is working to bolster its biotech profile, but when it comes to infliximab biosimilar uptake in Europe and the U.K., Ireland is coming in last place, alongside Belgium. From what I've heard, there is less than 10 percent uptake of infliximab biosimilars in the country.
The American Diabetes Association online support community reveals patient responses to CVS' decision to drop Lantus for follow-on biologic Basaglar. There are very few comments here, but it’s still important for the industry to see how patients are learning about biosimilars and payer’s responses to them. There’s what you would expect: Patients are turning to google to determine what a biosimilar/follow-on biologic is, and then sharing the explanation with each other. I was struck by one comment calling attention to the Lantus Solo Star pen, showing patients connect with the specific device. (Good to note for those of you looking to differentiate your products.)
News out of the CPhI conference suggests that interchangeability might not be what it’s cracked up to be. A question I’ve heard raised at every conference I’ve attended, and which was posed at the CPhI conference is “why is interchangeability deemed the holy grail by developers when 80 percent of all biologics are dispensed directly in the hospital setting and dictated by the physician?” According to Rakesh Dixit of MedImmune, this percentage is accurate. However, he claims:
Sometimes perception is more important than the actual reality.
Unfortunately, it seems we’re going to have to get used to the (incorrect) notion that interchangeability will make a biosimilar appear “better” than a non-interchangeable biosimilar. But an expert from Thomson Reuters shared some details that suggest the FDA’s decision to strictly outline interchangeability has its perks. Because the EMA has not designated how to carry out interchangeability:
This will raise questions as we see more biosimilar launches as to whether there will be interchangeability between biosimilar one and two, or just between the originator and biosimilar one.
According to Bloomberg BNA, Medicare policy advisers have presented some solutions which would help incentivize biosimilar use. Currently, there are several incentives and discounts available that stand to favor the brand treatments over the biosimilar. For instance, copayments are currently set up to remain the same for biologics and the biosimilar, which means there is no incentive to make the switch. In addition, the coverage gap discount program (CGDP), which requires a 50 percent discount from the manufacturer for patients within the gap, is not currently applicable to biosimilars. From Bloomberg’s report, it appears there is support for applying the CGDP program to biosimilars. But there’s also talk of sharing cost-savings with patients. As one expert described, A lot of pricing in the field is based on rebates, but a patient’s cost is based on a pre-rebate price. Can some of that rebate be shared with the patient?
A Drug Topics article poses some interesting questions about how a payer will approach RA biosimilars from smaller companies. Brand makers launching their own biosimilar units certainly have a financial advantage and a well-established reputation. But for small companies, Elan Rubenstein, PharmD, principle of EB Rubinstein Associates, asks:
What extent will payers be concerned with the product quality, depth of experience, and ability to provide sufficient quantity without stock-outs of small manufacturers, or manufacturers established recently, specifically to commercialize biosimilars, relative to well-known named manufacturers? How much lower must the net price of a small or new manufacturer’s biosimilar be to overcome payer concerns with small or new manufacturer quality, experience, and ability to supply product?...If a payer takes a leap of faith to contract with the cheaper biosimilar made by a small or new manufacturer, what might be the consequences should things not go as planned?
I would hope payers would consider these questions when approaching any treatment or company — not just a small company with a biosimilar. I take a bit of an issue with the phrase “take a leap of faith to contract with the cheaper biosimilar made by a small or new manufacturer” because that automatically discredits the FDA approval and the company’s analytical work, which would have undergone a stringent FDA review. At that point, it shouldn’t be a “leap of faith” in terms of a product or company’s quality. But it certainly wouldn’t hurt for smaller companies to be prepared to attest to the strength and reliability of their supply chains.
Why Biosimilar Makers Should Pay Attention To Archigen Biotech (10.7.16)
In preparation for Samsung BioLogics’ IPO, the Samsung group hopes to increase the capital of Archigen Biotech, creating a trio of Samsung bio companies — Samsung BioLogics, Samsung Bioepis, and Archigen Biotech. Archigen is currently at work on SAIT101, a biosimilar of Rituxan. The company is a joint venture by Samsung BioLogics and AstraZeneca. Since its founding, it has applied to the FDA for approval of a clinical test of SAIT101, which it scooped up from Samsung Electronics in 2012. As Business Korea explains:
Archigen Biotech began to develop a biosimilar product of Rituxan, making Samsung’s product lineup more various. In the case of Bioepis, the company does not have a biosimilar line-up of Rituxan due to Biogen, the original developer of Rutuxan. But Archigen Biotech is relatively free in this aspect so the company can build a complementary relation with Bioepis. Some experts say that Archigen may expand its business such as new drugs as it focuses on bio drugs unlike Samsung Bioepis whose main business item is biosimilar products.
There’s always a chance Archigen could swing to the innovator side of things, and AstraZeneca’s work in the novel biologics space could push the company in this direction. But AstraZeneca also has a foot in the biosimilars door in Asia, having established a 50/50 joint venture with Fujifilm and Kyowa Hakko Kirin called Fujifilm Kyowa Kirin Biologics (FKB) in the summer of 2015. The JV is currently at work on FKB238, a biosimilar of Avastin. Given AstraZeneca’s focus on immunotherapy, Archigen could be t gateway to the biosimilar oncology space and cheaper combination treatments. This could also be the company’s way of gaining a foothold in Korea, which would be beneficial given the country’s potential to bolster worldwide biologics and biosimilar development.
The country has made several steps forward in terms of new regulatory policy, and the low costs of biosimilars are pushing the market forward. However, as one expert told Business World, The local market for biosimilars is intensely competitive and will continue to be so, while the number of Indian companies that finally establish a foothold in developed markets will only be few. A recent Assocham report argues there needs to be more collaborative efforts if the market will be able to grow globally. Marketing collaborations have been particularly beneficial for Indian companies in the past, according to the report, which references the successful marketing partnerships the country has seen on DPP4 inhibitors for type 2 diabetes.
According to a Pulse article, over the next three to four years, Korea is set to produce one tenth of the worldwide biologic drug production. According to Udit Batra, CEO of life science at Merck:
Korea is currently producing around 5 percent of 4 million liter biologic drugs in the world but its production capacity will more than double within three to four years, when the global production will rise to up to 5 million liters.
As the Korean government releases plans to grow the biopharma industry, we’re also met with the news that several companies have built or are planning to build training centers in the city of Songdo. Following in GE’s footsteps, Merck just announced that it is also opening a bioprocessing collaboration center in Songdo.
Drug Price Wars Cause Turmoil In Insulin Space (9.30.16)
Novo Nordisk has announced 1,000 job cuts after lowering its 2016 growth forecasts. The company is citing sharp price cuts for diabetes treatments in the U.S., as well as increasing pressure from PBMs about pricing. After all, CVS and UnitedHealth recently chose Eli Lilly’s Basaglar for their formularies in place of Lantus and Toujeo — despite rebates of up to 60 percent for Lantus. Bloomberg anticipates more cuts coming from big insulin makers in the future. It’s going to be interesting to see how the competitive landscape changes when Basaglar arrives on the market. I haven’t heard anything about its price tag. But if innovators pre-biosimilars are already strained from discounts, we could be seeing some pretty steep discounts right off the bat for biosimilar insulin products.
The Nikkei Asian Review highlights the lengths Celltrion Chairman Seo Jung-jin went through to build the rising biosimilar company. Though Remsima, its infliximab biosimilar, is expected to garner $2 billion in annual revenue in the U.S. alone, there was a time when the company did not have such strong footing. According to The Review:
To fund the research, Seo tried to raise money by listing Celltrion on the Kosdaq, the country's startup-heavy, tech-centric stock market. But the company was relatively unknown at the time, and investors gave it the cold shoulder. Seo did not give up. He bought the company's shares by borrowing from private lenders who asked him to hand over various internal organs if he failed to pay them back. ‘I signed such contracts so many times, some lenders said I didn't have any organs left to be collateralized,’ Seo said in an interview with local media.
Apparently, the threat of losing one’s kidneys does wonders for an emerging biosimilar pure-play.
Or, could it just be problematic journalism? The Korea Times claims a transcript from a recent investor call suggests that Celltrion might be looking for another partner to sell Inflectra (infliximab). Apparently, the company has officially denied a split from Pfizer. However, according to The Korea Times, a company official claimed:
‘There are quite a large number of big bio pharmaceutical companies that are willing to sell Remsima for us.’… The remarks came in response to an investor inquiry on how Celltrion is dealing with the potential risks of Pfizer sticking to its own Remicade biosimilar that is under development. He said, ‘The contract between (Celltrion) Healthcare and Pfizer is, I believe, not that strong. It is, we believe, based on their own interest.’
Apparently, there are a number of large companies looking to become involved in some capacity with Celltrion’s biosimilars. But here’s where it gets confusing. One paragraph claims there was no clarification about whether these large companies were interested in deals over other candidates, or if they would be replacing Pfizer. Then, immediately in the next paragraph, an expert is cited stating that these companies are interested in other biosimilars, not Inflectra, and that there were no problems in the Pfizer partnership. This is the only time I’ve heard talk of a potential parting of ways here, so I’m going to guess it’s primarily speculation. I’ll be keeping my eyes open, however.
Amgen’s newly approved biosimilar for Humira will be boasting the title Amjevita (adalimumab-atto). As BioPharma-Reporter points out, there seems to be some sort of wordplay going on here. After all, the biosimilar name starts of sounding just like Amgen. According to reporter Dan Stanton:
Biosimilar makers have made it clear they want to avoid differentiating their copycats from the originator product. … Amjevita appears to buck this trend, and if it deliberately references its sponsor, then maybe it reflects Amgen’s unique position in the biosimilar market and its strategy going forward. … Perhaps Amgen is attempting to leverage its reputation as a maker of originator biologics to promote the quality of the biosimilar, with the name Amjevita serving as a gentle reminder to both prescribers and payers.
Stanton poses some interesting interpretations in this article, and, given Amgen’s presence in the innovator and biosimilar space, it wouldn’t surprise me if these branding theories hold water. (Amgen has not specified why it chose the name it did.)
After years of debate about splitting the company in two — one for new, innovator products and the other for generics — Pfizer has decided to stick it out as one. An analyst from Edward Jones & Co. told Bloomberg:
Right now, with drug pricing concerns, the bigger-size companies could have more advantage when it comes to negotiations [with pharmacy benefit managers and health insurers].
A senior portfolio manager from Turner Investments states:
In an environment where things are becoming a bit more sensitive in terms of drug pricing, I think more diverse entities like this provide investors more protection than the pure-plays.
There are two things that strike me about this article. For one, it continues to attest to the rising strength of PBMs, which is beneficial for the uptake of biosimilars. And, while I also agree, to some extent, the larger the company, the more fighting power it has, there is something to be said about smaller companies. If we’re thinking about biosimilar pure-plays, pricing can’t be too low right off the bat or else it would threaten the business’ stability. But the smaller the company, the greater likelihood of flexibility in their development. I talked to Oncobiologics recently, which argued the pure-play model offers greater flexibility in development. This then translates to greater pricing flexibility, which many of the larger companies cannot swing.
We’ve heard about Amgen’s triumphant FDA approval for the first Humira biosimilar in the U.S. And, because the patent landscape for Humira is so intense, we’ve also heard a number of estimations as to when this biosimilar will actually hit the market. In the midst of all that news, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER), denied one of AbbVie’s citizen petitions. This particular petition was arguing any biosimilar application referencing a BLA submitted prior to the initiation of the BPCIA would constitute a taking under the Fifth Amendment. This would, obviously, affect Humira biosimilars, as Humira was approved in 2002. Similarly, AbbVie argues the information included in a BLA becomes trade secrets upon approval, and those manufacturers filing BLAs prior to the BPCIA expected this information would not be used to benefit a competitor. The letter from Woodcock states:
Because the analytical, preclinical, and clinical data submitted by Abbott (AbbVie’s predecessor-in-interest of Humira) were available for public disclosure immediately following the approval of the Humira BLA, they are not properly entitled to protection under the Fifth Amendment. … When the Humira BLA was submitted and approved in 2002, Abbott did not show — and still has not shown — any extraordinary circumstances that justify nondisclosure of the safety and effectiveness data and information of the Humira BLA.
I’ve read some of the other citizen’s petitions from AbbVie, but I think this one takes the cake. I certainly give the company’s lawyers props for creativity.
Sanofi Takes On Merck’s Insulin Glargine Biosimilar (9.19.16)
Sanofi is claiming Merck’s biosimilar candidate, MK-1293, which was submitted to the FDA for review in August, is infringing 10 of the drug and device patents. According to PMLive, Sanofi’s Lantus has seen an 11 percent decline in sales from both biosimilars and competition from other brands. Interestingly, in the first half of 2016, Sanofi observed a 15 percent decline in sales. However, the decline in sales isn’t entirely because of the company’s biobetter, Toujeo, despite the company’s hopes that it would save the day. Some of the loss we can definitely attribute to Lilly’s and Boehringer’s biosimilar Abrasia in the EU.
According to The Pharma Letter, The Russian Ministry of Health is considering altering the tender system when it comes to public procurements of high-priced drugs (a.k.a. biologics) and vaccines. This move would also lead to several changes in which larger companies would end up edging out smaller companies. As the article describes:
According to the Russian legislation, currently no less than 15% percent of the total annual volume of drug purchases for state needs should come from small businesses… . The government believes that the necessary resources for the supply of expensive medicines and vaccines have only major suppliers, so they should only be able to work in this market.
There are arguments that the high cost of making and storing drugs can only be accomplished by larger companies. But there are some concerns there will be less competition within the country. Seeing the attention being paid to the BRIC nations for the future of biosimilar development, I’m curious of the implications here for biosimilar makers. These new conditions could bode well for Biocad within the country. But also in the list of companies standing to benefit include Pfizer and Novartis, which are major suppliers of costly drugs and vaccines to the market.
Leerink Partners have expressed some good news for reference makers, and some less great news about market uptake for biosimilars. As FiercePharma reports, Amgen’s Enbrel and AbbVie’s Humira will continue to fend off biosimilar competition over the next few years, regardless of emerging biosimilars. In fact, by 2022, analysts expect Enbrel sales will reach $6.7 billion and Humira will hit $15 billion by 2022. This is also made more likely because one analyst says:
He sees ‘limited cross-over competition between biosimilars of one molecule and residual branded sales of another’— meaning that copies of fellow blockbuster Remicade aren’t likely to encroach on Enbrel and Humira’s territory.
I’m curious to see how this cross-over competition theory plays out. From what I’ve heard from payers, there are mixed views on how this would work out. Some seem to believe that the release of Enbrel and Humira will serve as competition to infliximab, which suggests there will be cross-over potential amongst these meds.
The Prescription Benefits Manager (PBM) has announced its plans to treat anti-inflammatory conditions separately (i.e., psoriasis, rheumatoid arthritis, Crohn’s disease). In addition, it’s also launching an educational initiative to ensure patient adherence to biologics, such as Enbrel and Humira. Should a patient discontinue any anti-inflammatory drug, Express Scripts will refund up to $6,000 within the first 90 days. (There is a similar value-based program in place for diabetes treatments as well, which could impact the growth of the insulin follow-ons as they come to market.) As FiercePharma writes:
Drugs for Inflammatory disease have traditionally been lumped together in formularies, even though are made up of different conditions that range from rheumatoid arthritis to skins conditions like psoriasis, to Crohn's disease, which is an inflammation of the bowel. Express Scripts intends to treat each condition separately, with meds approved for each one. That will allow it to pit niche drugmakers against those that make non-specific drugs to extract bigger discounts.
Missing from this announcement was how the PBM plans to address the biosimilars coming to market. From what I understand, there will be individual formularies for each of these indications, so treatments only approved for one particular indication rather than all of them (like Humira) will have a chance to compete in the market and drive prices down. So far in the biosimilar realms, the FDA is in favor of extrapolation for all of the biologic’s indications. A biosimilar that wasn’t approved for all indications might raise some eyebrows over its quality. But a formulary structure such as this does leave the possibility open for biosimilars that are only approved for a select few indications to stand a chance on the market.
Medscape published a Q&A between two physicians discussing the process of creating biosimilars, the purpose of clinical trials, and the current regulatory hurdles. In terms of pricing, the interviewee discussed the current pricing being anywhere from 25 to 30 percent. However, he also acknowledges that, as the market grows, this discount is only likely to grow.
What will happen is that by the time we are starting to produce more biosimilars, the technology will improve, so the cost of goods will decrease. Maybe three years from now, they will refer to [this] discussion about 30 percent as rubbish, because it will be 50 percent.
There’s been a lot of focus on Norway and its 70 percent discount for biosimilars. Many have looked at this figure in awe, making the argument this will likely not be feasible for a sustainable market. (In fact, the doctor being interviewed by MedScape also expects discounts this steep to be unrealistic.) But the word from Sanford Bernstein analyst, Ronny Gal, is that the U.S. and biosimilar makers should start picturing a future with 75 percent discounts as the norm.
As LiveMint reports, Dr. Reddy’s has launched new designs for five of its generic brands in India, and the company plans to roll these out to 25 more brands moving forward. Most of these drugs include the company’s syrup bottles and blister packs, which won’t be relevant to the company’s biosimilars. But the reasoning behind this got me thinking about the issue of biosimilar labeling. As Dr. Reddy’s states:
Traditionally, pharma packaging has been designed to meet technical and regulatory requirements and not so much to address patient convenience.
There’s a similar argument in the biosimilar space about the inclusion of comparative data in the label. But besides catering to patients, for biosimilars it’s going to be even more important to cater to the physician. (Physician centric?) Physicians have been some of the loudest proponents of seeing the comparative data between a biosimilar and biologic. But from what I’ve heard from doctors attending biosimilar shows, this kind of data isn’t always clearly understood by this audience, and the analytics are where it’s at in biosimilars. (And putting comparative analytics data into a label is definitely going to add even more confusion.) As Bert Liang, chair of the Biosimilars Conference, said at a recent GPhA biosimilar conference, the industry’s charge (and main challenge) is putting what it knows about the science of a biosimilar into patient and physician friendly terms. Perhaps one of the places to do this is on the packaging or in the label.
Clinton Cracking Down On Drug Pricing (9.2.16)
FiercePharma highlights the plans Clinton has laid out to discourage high drug pricing. The most notable of these plans is the launch of a drug price oversight group. Fierce writes:
The group would scour for “outlier” price increases, accounting for a treatment's production costs and its value to patients. If the panel identifies an “excessive, outlier price increase,” Clinton proposes enforcement tools that include fines on offending drugmakers, emergency importation of newly pricey products, and measures aimed at increasing competition.
If Clinton is elected, it will be interesting to watch how the panel will impact the pricing of biosimilars. Especially for biosimilars to Enbrel, which was first approved in 1998, or biosimilars of rituximab, which could face threats from biobetter Gazyva, a panel like this could pressure biosimilar makers to implement steeper discounts right off the bat. Overall, the whispers I'm hearing out there suggest Clinton could be carrying us toward price-capping akin to what we see abroad. But how seriously should pharma take these plans? According to Fierce, Pfizer CEO Ian Read seems more concerned about the House and Senate, and he doesn't expect that Clinton’s plans will completely sway Congress.
A new survey taken by the European Federation of Crohn’s and Ulcerative Associations was recently published in the Journal of Crohn’s and Colitis. According to the online survey of 1,181 Crohns, IBD, and colitis patients, only 38 percent had heard of biosimilars. Only 25 percent of participants had no concerns about taking biosimilars. Reuters reports:
When researchers asked these 383 people [who were familiar with biosimilars]more questions to see what they knew about these medicines, 47 percent said they worried about whether the copies were safe and 40 percent said they had concerns about whether the generics were effective, researchers report in the Journal of Crohn’s and Colitis.
A couple of other key stats to take away here include: 66 percent of patients desire transparency over whether they’ve received the biosimilar or brand. Only 13 percent felt that extrapolation of a biosimilar makes sense, but the concept of interchangeability seems to have garnered patient trust. Interestingly, only 21 percent would be against the notion of interchangeability if the patient was not aware of the switch occurring. (Perhaps also of importance, the study was funded by a drug industry grant, and the writers do have financial ties to reference product sponsors. The population was also classified as “unknown,” which could have biased results.) But once again, these responses (minus the interchangeability stat) are not entirely surprising, given patient groups’ continued emphasis on the need for biosimilars to prove their safety and efficacy.
It shouldn’t come as any surprise given recent FDA and EMA approvals of new biosimilar candidates that Celltrion is now facing competition. According to The Korea Herald, the company’s core competitiveness comes from being a ‘first mover.’ But now, the company faces competition in the EU from Samsung, which recently had its infliximab biosimilar, Flixabi, approved. The Herald reports:
As of the second quarter of 2016, Celltrion’s Remsima had taken away some 40 percent of the original’s sales in Europe as the only Remicade biosimilar available in the region, the company said. And it claims it can drive this number up to 50 percent by the year’s end. … Analysts say Remsima’s performance is impressive, yet limited in scope. Celltrion’s replicated drug has had little impact on the sales of blockbusters drugs Enbrel and Humira. … Doctors in Europe appear to be cautious in prescribing Remsima in place of other anti-TNF biologic drugs (including Enbrel and Humira).
The launch of biosimilars for Enbrel and Humira will, obviously, create more competition among the biosimilar and its reference product. But it could also build walls and cease competition amongst the different patient populations for each drug. For instance, we should expect that, as Enbrel and Humira biosimilars enter the market, the infliximab biosimilars will be more strictly limited to the Remicade market. Even though this article doesn’t present any ground-breaking big news, it’s still worth a read, because it gives a good breakdown of the current biosimilar pipeline and competition emerging in the EU and the U.S. over the next year or two.
I just wrote an article on comparator sourcing for biosimilar clinical trials, in which the expert discussed the willingness of most big companies to provide samples of their biologics to biosimilar companies. However, The Hill featured a column today about some of the difficulties generics companies in general are facing from reference companies. These challenges include obtaining reference product samples, as well the refusal to entering risk-mitigation sharing agreements.
As of January 2016 the FDA had already received more than 100 complaints from generic product developers that were unable to obtain access to samples of an innovator drug to compare and test their generic products.
I’d be curious to know what percentage of these developers were biosimilar companies. The article goes on to discuss the CREATES Act (Creating and Restoring Equal Access To Equivalent Samples), which aims to enforce the FDA Act amendment specifying brand manufacturers may not “block or delay” generic drug applications. But there is nothing set up to help enforce this amendment. Overall, we need to see some sort of framework to ensure generic makers gain the right to launch a judicial injunction or to receive monetary damages for any drug that got held up by a reference company--and this is what the CREATES Act is aiming to do.
A few weeks ago, Napp went against the U.K.’s Prescription Medicines Code of Practice Authority (PMCPA) for holding a meeting for U.K. physicians in Norway about Remsima. This meeting went against the PMCPA’s code prohibiting drug advertising to U.K. physicians. Now, Napp and Hospira (Pfizer) have received similar reprimands. Hospira held what was deemed an “improper” meeting in Zagreb, Croatia, while Napp paid doctors to attend an “advisory board” meeting in London. FiercePharma reports:
The PMCPA panel said the [five-star] hotel ‘was not appropriate’ and that it had been billed as ‘the finest hotel in Zagreb.’ The panel also wondered whether it was really necessary for ‘health professionals to travel to Croatia to be reassured about the manufacturing quality of Hospira products,’ the PCMPA case report states. ‘[D]etailed information about the manufacturing facility could have been incorporated into a meeting held in the U.K.,’ the panel added.
In Napp’s case, ‘The meeting objectives were very much about how Napp could improve the uptake of Remsima in NHS London…’ The report cites the ‘unbalanced nature of the presentation’ at the meeting, where the chairman lauded Remsima, also a biosimilar version of Merck’s Remicade, and said he intended to switch all his rheumatoid arthritis patients to the med.
We’re clearly going to be seeing a lot of more of these marketing-related issues in the future. Baseline message so far seems to be: Don’t invite U.K. health professionals to paid events within the U.K. or to any biosimilar-related events that do or do not pay participants outside of the country.
The medical journal Ann Rheum Dis published an article on the structure of biosimilar clinical trials. In the past, Phase 3 clinical trials for anti-TNF biosimilars have boasted several different designs. Though they had similar primary endpoints, efficacy was evaluated at different times. For instance, CT-P13 researchers evaluated efficacy at week 14, 30, and 54. The etanercept biosimilar approved in Korea in 2014, HD203, was at 12, 24, and 48 weeks. Each of these time periods occurs during the plateau phase of the time-response curve. This was compared to Samsung Bioepis’ SB4, which were examined at several earlier time points. The authors of the article write:
Since potential differences in efficacy are more likely to be detected during the rapid rise phase of the time-response curve compared with the plateau phase, assessment of efficacy at early time points is a more sensitive way of comparing a biosimilar with its bio-originator. This aspect of clinical trial design should be standardized for future studies of biosimilars. Indeed, it could be argued at a ‘standard’ clinical trial design be adopted for all biosimilars of a particular bio-originator in a given disease.
An interesting read for those in the clinical space.
According to STAT News, citizen petitions are still being used to delay generic or biosimilar competition, despite changes to guidelines several years ago to limit their use. Many of the petitions being submitted today do not raise valid scientific concerns and seem to have been submitted simply as a delay tactic. The issue is that the FDA is expected to review the petitions within 150 days, and if/when these petitions turn out to be a “competitive ruse,” this pulls regulators away from other high-priority agency work. STAT writes:
The concerns expressed by FDA officials largely mirror a forthcoming analysis, which was coauthored by Michael Carrier, a Rutgers University School of Law professor who specializes in intellectual property. The analysis found that brand-name drug makers filed 92 percent of such citizen petitions between 2011 and 2015, although the FDA denied more than 9 out of every 10 petitions.
We’ve already seen two citizen petitions from AbbVie concerning labeling and interchangeability. Just last month, the labeling petition was denied as the FDA said it plans to make the appropriate labeling decisions on a case-by-case basis.
Now that the Prescription Drug User Fee Act (PDUFA) has been laid out on the table, drugmakers have begun to offer their praise and suggestions of the outlined goals. AstraZeneca, for one, is specifically pushing for more access to the data accrued via Sentinel, the FDA’s postmarket surveillance system. RAPS writes:
[AstraZeneca VP of U.S. regulatory affairs and policy & global intelligence Howard Hutchinson] points out that the current goal letter commitments do not explicitly note intent to use Sentinel data in signal detection, only in signal evaluation. Sponsors should be informed if the FDA plans to use Sentinel for routine signal detection, as this will likely generate more signals that will require investigation by sponsors and more company resources devoted to this activity.
This suggestion is important for biosimilar companies, too, given the emphasis on adverse event reporting for biosimilars. Afterall, one CDER expert has emphasized that Sentinel could be used to study the switching between biosimilars and biologics.
Australia’s Pharmaceutical Benefits Scheme Committee (PBAC) has recommended that Brenzys, a biosimilar to Enbrel, be made available to patients, as well as ‘a’ flagged for pharmacy level substitution. (This biosimilar is known as Benepali in the EU.) Australia is the first and only nation to come out in support of pharmacy-level substitution of biosimilars. However, as The Pharma Letter writes:
The PBAC noted that the substitution process allows for patient and prescriber choice and is not automatic. For any individual prescription, a prescriber may choose to not permit brand substitution. If substitution has been permitted by the prescriber, the patient may choose which brand they wish to receive from the pharmacist.
‘A’ flagging is still disquieting for Australian physicians. However, there is still a great deal of physician and patient control here. Even should the doctor not check the “substitutions permitted” box on a prescription, the patient is also allowed to voice their preference at the pharmacy — though my question is if this choice includes brand vs. biosimilar, or if it’s just brands vs. brands, or biosimilar vs. biosimilar. Either way, giving the patients the choice at the pharmacy counter would likely be a plus for the many concerned patient advocacy groups in the U.S. right now.
In his column for The Wall Street Journal, Scott Gottlieb, former FDA deputy commissioner, discusses some of the “regulatory policy blunders” that are making it problematic for generic firms to enter the market and price their drugs affordably. A big issue is that generic firms are expected to initiate the same costly requirements facing branded drugmakers. Gottlieb mentions the FDA’s push to simplify production lines and to increase the cost and complexity of completing a generic drug application. His suggestions emphasize creating more incentives for generics makers:
The FDA should prioritize applications for generic categories where competitors are exiting. Companies that pursue copies of ‘abandoned’ generics could receive a voucher that gives them expedited review of another generic drug. The value of this voucher would give firms more incentive to market copies of low-volume generics.
This article, though mostly focused on the small molecule space, is worth a closer look. As biosimilars begin to take off, I imagine there could be some carry-over of these efforts, though the pricing landscape — and, therefore, the financial incentive — is looking to be different for biosimilar makers. Overall, there seems to be a great deal of pride associated with companies making generics these days. I’m thinking specifically of Teva’s recent application and inclusion in PhRMA, as well as the arrival of biosimilars, which are carving out their own space in the innovation spectrum. It makes sense that the industry should move in the direction where it incentivizes the development of generics, including biosimilars, just as novel drugs in overlooked therapeutic areas are incentivized.
It seems like Celltrion’s predictions of launching its Remicade biosimilar Inflectra on October 3 are close to coming true. The District of Massachusetts Federal Court has ruled that one of J&J’s patents on Remicade is invalid. The patent, known as ‘471 protects the anti-TNF-alpha’s mechanism of action, which was set to expire in 2018. In preparation of a U.S. launch, Celltrion has announced its beginning to ship the biosimilar to the U.S. However, J&J isn’t quite done fighting yet. The company plans to appeal this ruling, as well as a similar ruling on the same patent made by the U.S. Patent and Trademark Office. In addition, one lawyer told BioPharma-Reporter that J&J also has patent protection over the culture media used to product infliximab, which doesn’t expire until 2027. This patent is still being considered in court.
Somethings to keep in mind, however: Should Inflectra launch and J&J finally win the appeals, Celltrion/Pfizer would be responsible for reimbursing J&J for any profits lost from the biosimilar competition. These ongoing legal battles could also make payers skittish about placing Inflectra on their formularies until the challenges have been resolved. If the launch does go through, however, I’d be very curious to see if CVS revises its formulary to include Inflectra, since it’s been particularly gung-ho about ensuring biosimilar uptake in 2017.
I had the good fortune of stumbling upon a release on Twitter discussing the first Belgian Biosimilars Conference. The uptake of biosimilars in Belgium has been low because the prices of biosimilars drugs and the reference drug following patent expiry tend to “fall about equally”. The translated document is a little choppy, but it sounds like the country’s goal is to see at least 20 percent of patients treated with biologics switched to a biosimilar by the end of 2016.
The part that caught my attention, however, was a testimonial from a “representative of a patient” (perhaps a doctor) who stated:
Nobody has informed me that there [there is such] thorough research into biosimilars. The message that biosimilars must meet the same requirements of quality, efficacy, and safety as any other drug was new to me. I look at biosimilars now with completely different eyes.
It should come as no surprise that the major takeaway from this event was: education, education, education. (Sound familiar?)
As RAPS reports, this new guidance doesn’t introduce any new requirements. However, it’s worth reviewing, given the intense focus on biosimilar pharmacovigilance in all the markets. Overall, the guidance emphasizes paying attention to immunogenicity and including this in risk management plans. Companies also need to keep in mind the number of manufacturing changes that occur and consider updating the risk management plan. When it comes to the drug landing in patients’ hands, the guidance stipulates that healthcare professionals should provide patients with the drug’s product name and batch number. This will be particularly important when switching patients to biosimilars.
The Pharma Letter examines how reimbursement works in the U.K., Germany, Japan, and the U.S. markets. As I’ve discussed in recent articles, it takes more than just getting your drug approved to see success on the market — especially in the U.S. It now relies heavily on building a relationship with payers. The organizations discussed include N.I.C.E in the U.K., Germany’s Institute for Quality and Efficiency in Health Care (IQWiG), Japan’s Ministry of Health, Labor, and Welfare (MHLW). The U.S. currently lacks a formal Health Technology Assessment (HTA), because of the fragmented payer landscape.
The article provides descriptions of how each nation determines the cost of new drugs on the market. Despite some of the challenges facing the U.S. because of its fragmentation, it currently isn’t the most difficult reimbursement landscape.
While it is important to recognize the US ‘payer’ scrutiny is rising rapidly, the biggest access challenge still lies in Europe. In Europe today, companies are facing an intensification of the ongoing assessment of their product’s outcomes and value. Payers are increasingly commissioning their own research rather than accepting the manufacturer’s approach to the evidence. The U.K. is leading the move towards this model and the industry is wary of where it will lead.
Moving forward, there is going to be just as much pressure in the U.S. If we think about the latest news about CVS, Sanofi has agreed to lower the price of its Lantus, however this reference drug was still excluded from the formulary in favor of a biologic. It was the same in the hepatitis C battles beginning in December 2014. Though Harvoni came with the support of the community and was user-friendly, there was not enough justification of the price.
Medscape highlights the progress being made by Intas Pharmaceuticals on its Lucentis biosimilar. Between July 2015 and 2016, there were 4,668 injections of the biosimilar administered following a ban of bevacizumab (Avastin) in India. However, 10 percent of patients that received an injection from the first three batches of the Lucentis biosimilar experienced inflammation. Not all is lost here, though; The company has since added an additional filtration step to its manufacturing process, as well as fresh “ultrapure Polysorbate 20”, Medscape reports. From batch four and on, there were no significant adverse effects reported following a small, short-term clinical trial. The company hopes to conduct Phase 3 trials to gain approval in the U.S. and EU.
It shouldn’t come as a surprise that some physicians are skeptical about how this drug would perform in the U.S. Not only would quality concerns be an ongoing issue, but the drug also faces competition from Avastin. If the industry has learned anything about Roche’s strategy to compete against biosimilars, it involves aggressively lowering the prices of their biologics. In this case, Genentech manufactures both Avastin and Lucentis. These lower prices for a solid reference drug could easily trump a biosimilar with a history of adverse effects in India.
BioWorld published a great column today about the implications of allowing biosimilars to launch on the market when the branded biologic still has patented indications. The article focuses on Humira. While legal challenges and patents could keep Humira biosimilars off the market for a while, the label on Humira is quite large. There will still be indications, for instance, uveitis, which will be protected through orphan drug exclusivity. As BioWorld writes:
While the FDA would likely carve out the protected indications, AbbVie has no guarantee that doctors and payers would honor them, especially if there’s a significant price difference between Humira and a biosimilar. … Cost savings are needed, but if payers and prescribers ignore carve-outs, they could chill the ongoing development of promising, multiuse biologics like Humira, leaving new indications for unmet medical needs undiscovered, untested, and unapproved.
BioWorld brings up a good point here: reference product sponsors are making some impressive moves to advance the labels of their drugs. Humira is currently listed in 140 clinical trials on ClinicalTrials.gov (only 3 of which are not yet recruiting patients). Amgen currently has Enbrel enlisted in 75 different trials. In the current market (especially in the U.S.), however, doctors are still concerned about extrapolation, let alone stepping away from the label altogether to treat the carve-out indications. So that fear, arguably, should be less pressing for the next couple of years. It’s also hard to imagine a biologics maker would simply “give up” pursuing additional indications, given the drive we see today to continually make candidates valuable and, therefore, harder ot replace.
According to LiveMint, Lupin is jumping into the biosimilar ring with Biocon and Dr. Reddy’s. The company expects to file its etanercept biosimilar for approval in Japan in 2017. The candidate is currently in Phase 3 trials. Following a submission to Japan, the company is planning EU and U.S. submissions as well.
In an interview with SMi group, FirstWord Pharma’s Duncan Emerton discusses the current state of the biosimilar pipeline. The most popular targets, accounting for 24 percent of the total number of development programs, are filgrastim, EPO-alfa, and rituximab. Trastuzumab is in fourth place, attracting 7 percent of development programs, followed by etanercept, bevacizumab, and adalimumab. Emerton states:
Since June 2015, there has been a 20 percent increase in the number of programs targeting the key mAbs and fusion proteins. As of June 1, 2016, FirstWord’s Biosimilar Index included 265 biosimilar mAb and fusion protein development programs, up from 220 in June 2015, an increase of 20 percent.
BioPharma Dive addresses the recent announcements from CVS and Express Scripts about their 2017 formularies. It's interesting to note how differently they’re choosing to approach biosimilars. While CVS cut the brand products from its formulary in favor of starting new patients on the biosimilar versions, Express Scripts kept Neupogen and Lantus on board. CVS has chosen to go straight into biosimilar territory, despite Sanofi’s willingness to lower the price of Lantus. For Express Scripts, however:
The PBM's Chief Innovation Officer Glen Stettin told BioPharma Dive that Express Scripts sees biosimilars as a tool to leverage drug originators and further bring down price of the branded drugs. ‘As the biosimilar manufacturers and the originating manufacturers fight over patents and delay things to market, there is still opportunity to secure significant discounts from the originating manufacturer and make a benefit more affordable,’ said Stettin.
Overall, Express Scripts was more conservative in its 2017 formulary. CVS excluded a whopping 155 drugs compared to Express Scripts’ formulary, which excluded 85 drugs. It’s interesting to see such different strategies being taken by PBMs. This just goes to show how fragmented the U.S. system in likely to be as these products begin entering the market.
In his panel at the World Biosimilar Congress USA, Express Scripts’ CMO Steve Miller emphasized how drugmakers need to have an in-depth understanding of patient populations’ needs from their biosimilar. A company should have a strategy to incentivize patients to choose the biosimilar over the brand. Today, there was a good example of this. FiercePharma reports Sandoz has launched a copay program for Zarxio patients called Sandoz One Source. Fierce describes:
The Sandoz One Source copay program covers upfront costs for patients, which means their first dose or cycle comes free of out-of-pocket expenses. Patients then pay $10 for each monthly dose or cycle, for up to 12 months. The assistance program is limited to $10,000.
Programs such as these are expected to draw more patients to generic/biosimilar drugs. Sun Pharma has seen success from its own copay program for its generic version of Novartis’ Gleevac. I think this is a great example of what Miller was describing. Providing patients with an outlet to save out-of-pocket expenses could be a big incentive for patients. But beyond that, it would provide patients an opportunity to experience and ultimately trust the biosimilar.
Modern Medicine had a great article about the pharmacist’s role in adding biosimilars to formularies. Pharmacists working on formularies often tackle the “practical issues” that might be overlooked by drug makers or the payer.
For example, [a university hospital pharmacist] said, her hospital was exploring the use of the biosimilar Zarxio (filgrastim-sndz) as an alternative to Neupogen (filgrastim) and discovered that Zarxio only came in syringes. That raised a red flag for its use in pediatric patients, who need a small amount of the drug, she said. It wasn’t clear whether the biosimilar Zarxio in the syringes could be divided into smaller doses in a sterile way. Neupogen, by contrast, came in vials. This situation spotlights the importance of sterility in formulary evaluations of biosimilars.
This issue was a big point of discussion at the World Biosimilar Congress USA. Zarxio was the first biosimilar to market, but it does not have a perfect record in terms of commercialization. The fact there was no clear cut way of delivering the biosimilar to pediatric patients is being considered one of Zarxio’s biggest mistakes. However, because Zarxio is the only filgrastim biosimilar on the U.S. market right now, there is not as much incentive to fix this issue. Competition will not only be beneficial in terms of price competition; it will help ensure these “practical issues” get more attention from biosimilar makers.
According to BloombergBNA, Amgen’s case against Hospira (Pfizer) is moving forward following a district court session held last week. Though Hospira granted Amgen commercial marketing notice of its Epogen biosimilar, Amgen is asserting this notice was premature. Hospira submitted this notice after the FDA accepted its BLA for review rather than after a market approval. (According to Amgen v. Sandoz, this 180-day notice does not begin until after the marketing approval of the biosimilar.) Hospira is now moving to dismiss this suit, arguing that the BPCIA did not grant Amgen the rights for a private cause of action for a declaratory judgment.
After CVS and Express Scripts announced their 2017 formularies, both of which emphasize the arrival of biosimilar insulin in the U.S., insulin-goliath Novo Nordisk has found itself trying to carve a space in the market. Right now, the company is placing its bets on Tresiba, which is currently in comparative trials against Sanofi’s Toujeo. As CEO Lars Sorensen said:
It is our anticipating and our expectation...that we will see a bifurcation of the basal market. There will be one group of products which would be viewed as similar. That would, of course, in particular, be Lantus and Basaglar because they are biosimilar...Based on our expectation, the switch data will be able to improve the label of Tresiba and then we will find Tresiba in a separate category of the basal market.
While this could turn out to be the case, it seems the threat of biosimilars is already doing work on the prices of innovators. In 2017, Novo expects that average prices for basal insulin and human growth hormone will be “moderately lower.” These expectations have also led Novo to lower its operating profits forecast. While the company originally planned to see upwards of 9 percent growth, it has scaled back to between 5 percent and 8 percent profit growth.
Carol Lynch, the chair of the European Generic Medicines Association provides an interesting takeaway for those of us in the U.S. that tend to look to Europe as a biosimilar success story. While the EU has had 10 years of experience with biosimilars, these countries are still facing their own growing pains. As she states:
You cannot necessarily pick up one methodology and plonk it in another place and it will be successful. Each system has to find its own way. You can find the commonalities and apply them, but the key is to find champions locally who can see the benefits and drive them through….If you look at examples where there has been an adoption of biosimilars, it is generally because you have had a local player — a physician or a payer — who is championing the benefit to the whole system not just their silo, and the incentives are aligned and in the right place.
Overall, this is a great article highlighting the work biosimilars have already done, while also showing why the market is still struggling to grow. I highly suggest reading all the way through.
AbbVie has filed a lawsuit against Amgen, claiming that its ABP 501 Humira biosimilar is in violation of 61 of Humira’s patents. The company is beginning the suit by addressing 10 of these violations, with more likely to follow should the FDA approve the biosimilar in late September. According to Bloomberg:
The lawsuit could keep biosimilars off the market if AbbVie succeeds in getting a court order against Amgen, said Aude Gerspacher, an analyst with Bloomberg Intelligence. She said the case could last two to three years not counting any appeals, which would extend the legal fight to 2020.
Ugh. Well played, AbbVie. I personally like the language AbbVie used in its complaint: In seeking to defend its copycat actions here, Amgen is speaking out of both sides of its mouth.I guess that’s one way to describe the growing number of biologics makers joining the biosimilar camp.
In comments on the recent draft labeling guidance, a number of big drugmakers, including Sanofi, AbbVie, Pfizer, and Amgen, have come out in favor of including biosimilarity and interchangeability statements in labels. However, surprisingly, those against the inclusion of these statements in labels are not restricted to generics or smaller pure-play companies. Rather, there are a few big companies in the lineup, including Merck and Boehringer Ingelheim. These players express concerns that adding these statements, which will not include essential scientific information, could confuse stakeholders and raise doubts as to the biosimilar’s safety. Similarly, excluding indications from the biosimilar label might lead doctors to believe the FDA rejected the company’s application to treat that illness, when, in reality, that indication could simply be covered by unexpired orphan exclusivity.
Though I tend to agree more with the Merck’s and Boehringer’s in this battle, I get a general feeling that, come the final guidance, biosimilar labels will include both the biosimilarity and interchangeability statements. The FDA has been pretty good about balancing demands in their guidances. The biosimilarity statement and information on extrapolation might have to be biosimilar makers’ compromise for (potentially) being allowed to rely on the originator’s data. Sandoz’s Mark McCamish makes a great point about the just how much data should be appearing in a biosimilar label in this BioPharma-Reporter article. The introduction of non-clinical information in a label could suggest to a doctor that the biosimilar differs greatly from its reference product:
The label itself informs the doctor how to use the product, so if there is any change in that product use, or a different indication then you revise the label. What it doesn’t do is provide the regulatory history or development history of the product: which pathway did it go down, what decisions were made by the analytical data, and that’s a key thing. What good would it be to have a size exclusion chromatography [SEC methodology] in there when the doctor has never seen an SEC?
The world is in dire need of some more cost-effective diabetes drugs, and England, in particular, is feeling the pain from insulin treatment costs. According to The Pharma Letter, England primary care services are paying upwards of $1.33 billion for diabetes treatments. Compared to 10 years ago when 27.1 million items were prescribed for diabetes, over the past year, there have been 49.7 million items prescribed. Insulin has cost the National Health Service (NHS) 434.7 million pounds from 2005/06 to 2015/16. But the innovator insulin market is still alive and well, as PMLive reported today. Novo Nordisk saw a 161 percent increase in Tresiba (insulin degludec) sales following its first six months on the market. The company’s other insulin combo products have helped bolster sales by 7 percent.
I’ve heard very little about biosimilar uptake in Italy, and based off the revisions to this document, I understand more of why the country flies by under the radar — and why it likely will continue to be that way. According to The National Law Review (NLR), the Italian Medicines Agency has always left the choice to switch to a biosimilar on a case-by-case basis and in the physician’s hands. There is no automatic substitution in Italy. However, in its recent revisions, The NLR writes:
The Concept Paper does not state anymore that biosimilars ‘should be preferred – where they constitute an economic advantage – in the treatment of naïve patients.’ Instead, the Concept Paper now indicates that ‘biosimilars constitute a therapeutic option whose risk-benefit balance is identical to that of their originators.’ The Concept Paper states that this also applies to non-naïve patients, but specifies that in this case ‘the opportunity of the change is left to the clinical assessment of the physician.’ This suggests that AIFA is open to more biosimilar switching in non-naïve patients.
This might leave the option to switch non-naïve patients in doctors’ hands, but without payer pressure, this is unlikely to be the case. When it comes to biosimilars in Italy, uptake of Filgrastim was slower because payers took a backseat to urging a switch. There were also fewer incentives for doctors and patients to switch. For Epoetin alfa, payers in Italy have added some pressure to get doctors to make the switch, so the uptake in Italy has seen some increases. In fact, according to GaBI, sales of biosimilars began reaching a steeper pitch in 2012 and 2013, likely as a result of this pressure. The revision to Italy’s Concept Paper could mean the country is becoming more comfortable with the notion of switching in non-naïve patients. But unless payers get involved early, this change in use will be slow.
According to Bloomberg, Biogen’s current “leadership vacuum” following the retirement of its CEO and several other senior managers makes the firm a prime target for an acquisition. There has reportedly been some (unconfirmed) interest from Merck and Allergan, both of which are also at work on biosimilars. Bloomberg points out that a merger between Merck and Biogen doesn’t make the most sense in terms of their pipeline. If we think about this from a biosimilar perspective, Merck is already partnered up with Biogen and Samsung’s JV Samsung Bioepis to develop and commercialize several biosimilars. Allergan on the other hand has an Erbitux, Avastin, Herceptin, and Rituxan biosimilar in its pipeline. Hypothetically, these could partner nicely with the anti-TNFs Biogen currently has on the market (Flixabi and Benepali).
Sandoz and Eli Lilly/Boehringer Ingelheim got a huge boost when CVS Caremark announced it is cutting Neupogen and Lantus from its 2017 formulary. Zarxio and Basaglar will be taking their place, effectively ushering biosimilar switching into the U.S. setting. (Though, to be clear, Basaglar was not approved using the biosimilar pathway, and, as such, is technically a follow-on biologic.) Express Scripts took a more conservative approach to its 2017 formulary, leaving Neupogen and Lantus on its list of covered meds. However, the company did note that the list of preferred products will be “reassessed later this year to reflect anticipated product launches.” So Basaglar is very likely going to be in the picture.
CVS Caremark’s move to eliminate Lantus from the formulary was very bold, especially seeing how Basaglar has yet to even make an appearance on the market. What took me by surprise here is just how quickly CVS has moved. Though we do have evidence of Zarxio’s performance in Europe, there’s been little spoken about the drug’s performance so far in the U.S.— it has only been on the market for less than a year. (Though, this move will certainly give us more data to work with.) Similarly, Basaglar will not be available until December of this year, so it will hit the market and then be on a preferred formulary a few weeks later. In recent advisory committee meetings, patients have expressed that these decisions, driven by cost, will come in the way of the doctor/patient relationship. There have been concerns about extrapolation and about the act of switching overall. As such, CVS’ actions feel particularly aggressive when considering the current plod of the U.S. biosimilar market. But from a biosimilar market perspective, this move is what is needed, especially during the early educational phases, in order to ensure a swift uptick in the market and more widespread use and comfort.
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) cracked down on a session held in Norway about Remsima. According to RAPS, this meeting, which was supposed to be an informational session on Norwegian clinicians’ experiences with Remsima in IBD, turned out to be an inducement to prescribe or recommend Remsima. Also at issue…was Remsima market material calling for a switch from Remicade to the biosimilar Remsima. Ultimately, the meeting went against the U.K. Prescription Medicines Code of Practice Authority’s (PMCPA) Code of Practice, which prohibits advertising of prescription-only medicines.
The Appeal Board considered that whilst the location of the meeting [in Norway] was unacceptable, the aim of the meeting was not unreasonable…The [PMCPA] found that holding a two day promotional meeting in Norway without a clear and cogent reason constituted an inducement to prescribe or recommend Remsima, in breach of the Code.
It seems the primary issue here was calling U.K. physicians to Norway for this meeting. But this experience also demonstrates the different ways countries approach biosimilars. In making Norway’s hospital tender responsible for covering biologic treatments, the country pushed physicians to become a more responsible and active party in saving money for their hospitals. As such, there’s going to be more urging from management to make the switch, which clearly didn’t jive with the U.K.’s approach. As more countries become comfortable with the act of switching, it’s only going to become more difficult for doctors to avoid subtle promotion of switching when learning about the biosimilar versions of drugs.
Johns Hopkins University and Brigham and Women’s Hospital set out to determine how anti-TNF biosimilars compared to their reference drugs. After reviewing 19 studies, the researchers determined the biosimilar versions of Remicade or Humira were interchangeable with the reference products. The results were published in the Annals of Internal Medicine. Some experts, upon reviewing the study, have agreed the studies were valuable in creating more confidence in biosimilars. However, there are concerns that the study did not include a large enough grouping of patients. Others found the results reassuring, but not particularly surprising.
‘Honestly the data have been pretty consistent,’ said Dr. Daniel Solomon, a rheumatologist at Brigham and Women’s Hospital in Boston who was not involved in completing the review. ‘So I’m not sure we learned something new … but it does give confidence that indeed there’s a good margin of safety and the risks are minimal.’
Solomon voices my thoughts exactly here. The 10 years of experience with biosimilars abroad, and particularly the success in Norway and Denmark, have been indicative of everything these researchers discovered. If anything, it seems to be a method to push the U.S. market forward more quickly because of the reports conclusions of "interchangeability." This term is quite controversial and will carry a lot of weight for biosimilar makers and patients alike.
Ixekinumab Earning Psoriasis Doctors’ Attention (7.29.16)
Though Eli Lilly’s drug Talz, or ixekinumab, has only been on the market for a month, nearly one-third of surveyed doctors have switched patients from anti-TNF agents. Patients were also snatched from Stelara and Cosentyx. Ixekinumab is an IL-17 inhibitor. According to the release:
Current users expect their use of Talz to more than triple in the next three months, while during the same time frame more than 20 percent of non-users expect to initiate trial.
Though it’s possible that patients being switched to IL-17 inhibitors don’t respond to anti-TNFs, this doesn’t bode well for uptake of anti-TNF biosimilars.
Alexion is pulling out all the stops to keep Soliris biosimilars at a distance. According to BioPharma-Reporter, the company has filed new patents around the drug’s indications, methods of use, and manufacturing methods. Alexion is also patenting its commercialization methods. But similar to Roche, Alexion also seems to be setting its sights on a biobetter. BioPharma-Reporter writes:
Alexion is also developing a longer-acting C5 antibody, ALXN1210, to treat the same indications as Soliris. The candidate is in Phase1/2 clinical studies, and Alexion is targeting an approval date in 2018 for the PNH indication.
Along with new administration methods, biobetters are proving to be a popular method of extending a brand name drug. Biosimilar makers should heed this news, but I daresay by the time 2020 comes rolling around and soliris biosimilars hit the market, the environment will be much more biosimilar-friendly. As such, I'm doubtful that a biobetter version will provide sustaining value for Alexion.
Johnson & Johnson remains unconvinced. Even though a lab Celltrion used to manufacture Inflectra is currently being sued by J&J, Celltrion still anticipates launching its infliximab biosimilar in the U.S. this year. According to J&J CEO Alex Gorsky, 70 percent of the 2.4 million patients treated by Remicade have been successfully treated, and therefore, are unlikely to be switched to a biosimilar version. Pharma Exec writes:
This could mean that for 30 percent of the 2.4 million patients currently on Remicade, approximately 720,000 could feasibly be switched to Inflectra or another biosimilar of Remicade. In addition, new patients who are Remicade-naïve could be added to the patient population as eligible candidates for a biosimilar.
Gorsky has been particularly vocal about how the biosimilar and generics markets will differ, and that patients effectively treated by Remicade will not be switched from brand to biosimilar. But if we’ve learned anything from Europe, switching from a brand to a generic is not done for medical reasons, and biosimilars in pro-switching nations have come to trump brands. Patient groups and physicians are concerned that payers will get in the way of the patient-doctor relationship. But as long as the biosimilarity, safety, and efficacy are all in line with the brand drug, and switching is permitted, Gorsky’s predictions likely won’t be accurate.
GE has had some good luck in the past year with uptake of its modularized bioprocess facilities. According to the company’s CFO, We believe these modularized bioprocess facilities will be the future of all biologics. So far, JHL and Pfizer have secured deals for their Chinese facilities, both of which will be used to manufacture biosimilars. These are the only two companies right now (that I know of, anyways) that have chosen to implement this kind of system for their biosimilar production. I'm curious to see if the uptake of modularized facilities becomes a trend among biosimilar makers in particular.
Biosimilar makers are going to be seeing a sizeable discount starting in 2017. According to RAPS:
The fee for an NDA requiring clinical data or a biosimilar application requiring clinical data will be $2,038,100, which is $336,100 less than the $2.37 million fee from 2016. For an NDA not requiring clinical data or a supplement requiring clinical data, or a biosimilar biological product supplement with clinical data, the user fee is $1,019,050, which is $168,050 less than the fee for 2016. Establishment fees for 2017 will amount to $512,200, which is $73,000 less than 2016, and the 2017 fee for a new prescription drug or biosimilar product is $97,750, which is $16,700 less than 2016’s fee rate and more than $6,000 less than the fee for 2014.
This is great news for companies, but the question remains if these discounts have come at an appropriate time. The decreases in fees were brought about because of the growing number of applications. One of the primary concerns about the existing review process is the length of time it takes, and the FDA attributes this to a lack of employees. Discounts and a growing number of applications are great news for the growing market. But if the FDA is taking in fewer resources, this raises concerns about whether review delays will continue because discounts will keep the agency from hiring the appropriate number of employees it needs to meet the increasing number of biosimilar applications.
Both Teva and Mylan are presumably eying a generics joint-venture in Brazil, called Teuto/Pfizer, owned by Pfizer and Brazil’s Melo family. According to Reuters:
The sale underscores the challenge facing generic drugmakers in Brazil, where a weaker currency has stoked raw materials costs and the harshest recession in eight decades has slowed sales.
Brazil is arguably one of the most promising markets for biosimilar makers. The biosimilar and generics markets are obviously different. But issues with currency will also likely cause cost challenges for companies looking to develop and launch biosimilars in the country.
FiercePharma reports that Life Sciences Minister George Freeman has been reassigned following the Brexit vote. There has been no word yet of who will take over his position — or even if there will be a new life sciences minister appointed in his place. There are concerns the position has been eliminated altogether. Among his advocacy efforts for the industry, Freeman was responsible for establishing a working group headed by AstraZeneca and GSK CEOs to advise on the EU exit. Both AZ and GSK are taking the stage this week to announce their intent to remain in the U.K. However, the loss of a minister, though seemingly small, comes at a bad time for the nation. In the U.K., life sciences advocacy will be key — especially for the emerging biosimilar market. There are, of course, groups such as the BGMA and British Biosimilars Association to help advise and lead the charge on biosimilars. But having an advocate within the government would’ve certainly helped keep the biosimilars mission, as well as the sustainability of the U.K. life sciences, at the forefront.
A National Law Review (NLR) article argues that the recent Amgen vs. Apotex decision does not suggest that biosimilars will be approved using the tentative approval process often used for generics approvals. In the generics realm, tentative approvals are applied when a generic is found to be approvable prior to the expiration of the originator’s patents. However, these approvals require the applicant to reapply for approval 90 days before it could be released, even though the drug likely hasn’t been changed. As the NLR writes:
The Federal Circuit does not appear to have been contemplating this two-stage “tentative” approval process, but rather appears to have been suggesting an early approval process that would be inconsistent with past and current FDA drug approval practices.
The issue arose from a discussion of if the FDA has the authority to grant pre-effective date license approvals. This is in response to concerns that the requirement for the 180 commercial marketing notice will grant the reference product another 6 months of exclusivity after the biologic’s 12 years is up. The court deciding Amgen vs. Apotex seemed to believe the FDA could issue a license at the 11.5-year mark, which would mean the 6 months of exclusivity would end upon the 12-year date.
The author of the article proposes two surprisingly “black and white” solutions to this: creating a mechanism and writing a rule granting biosimilar applicants pre-effective date approvals. Or these pre-effective date approvals could be granted to biosimilar licenses without any written regulations. The author concludes, naturally, that neither of these is appealing given the first’s lack of timeliness and the second’s ability to spark additional law suits against biosimilars. Based off of this, I get the sense we’re going to be hearing more about this in the future—hopefully in the Supreme Court, if Sandoz gets its way.
Earlier this week, Pfizer announced it is at work with NovaMedica on a new manufacturing plant in Russia. The goal is to have the facility up and running by 2020. According to FiercePharma, NovoMedica will be licensing technology for more than 30 products in the cancer and inflammatory disease spaces — a majority of which are on the country’s most essential medicines list. The fact that NovoMedica has a line of products and candidates for gastroenterology and inflammatory disease bodes well for more biologics — and hopefully biosimilar — manufacturing in the country.
I remain optimistic that this plant is being built at the best possible time for the country, judging from the decline in drug sales in Russia. According to The Pharma Letter, sales in 2016 have already dropped by 10 percent, or $4.1 billion. Patient demand in the country has been falling over the past few quarters because a number of them are facing declining incomes. As such, patients have begun to avoid mid- to high-priced drugs. If this is the case, the country should be welcoming biosimilars and their makers with open arms, as long as there is adequate competition to keep prices low. That's going to be key here, because even if biosimilars are mid-priced, economic stagnation in the country is bound to keep that market from growing as well.
After Sandoz’s triumph in its etanercept biosimilar AdCom last week, the company tried to quietly eek out some not-so-great-news in its earnings report. The company received a complete response letter for its pegfilgrastim (Neulasta) biosimilar from the FDA. However it has yet to share any reasons why the application was returned to them for more work. Sandoz still expects it will meet its goal of launching five new biosimilars by 2020.
This decision has, not surprisingly, caused many in the industry to speculate about the FDA’s reasonings behind the CRL. It has also led to concerns about the state of the approval pathway. As FierceBiotech writes:
This will be a blow to the company and perhaps more widely to other biosimilar manufacturers, just when it looked like the regulatory side of things was becoming a little more predictable.
Despite the FDA’s concerns, the EMA accepted the application for review back in February, which makes the FDA’s reticence quite frustrating (as well as the lack of harmonization between these two huge regulatory bodies). But if we try to look at this more positively: should the application go on to be approved in the future (which it likely will), this primary stumbling block should reassure biosimilar naysayers about the soundness of the regulatory process.
According to Seeking Alpha, a number of analysts (sellside, primarily) are avoiding making predictions about the biosimilar market. This is because a majority of biosimilar development programs are underway in small companies that are not covered by bank analysts. EvaluatePharma has predicted the market will hit $7 billion by 2022, with the greatest help from Humira, Lantus, and Remicade biosimilars. But these products are often already on or near the market, and many of them have been manufactured by bigger players. As Seeking Alpha writes:
Only a third of the Phase 3 pipeline is in the hands of the sort of company that bank analysts would typically cover. This means that a huge proportion of late-stage development is ongoing in companies that the financial industry does not monitor particularly closely.
Roche’s biggest hope of competing against biosimilars did not live up to expectations in untreated diffuse large B-cell lymphoma. Gazyva, a biobetter to rituximab, has been a looming threat for biosimilars following Roche’s announcement that the biobetter was more successful in treating follicular lymphoma and chronic lymphocytic leukemia. But in this latest trial, a combination of Gazyva and chemo was not as effective as Rituxan plus chemo. As ENDPOINTS reports, That could leave the pharma giant vulnerable on one key front as biosimilars crowd in to claim part of a franchise worth $7.1 billion in 2015.
Last month at the Aspen Idea Festival, six former FDA commissioners argued in favor of putting some distance between the agency and the U.S. Department of Health and Human Services (HHS). (The FDA is currently part of HHS.) One former commissioner argued that making the FDA its own entity would facilitate one-on-one discussions with Congress and the White House without excess political and administrative interference. This isn’t to say that the FDA would ever be completely separate from the White House. But to grant it cabinet-level status would provide the current FDA commissioner better access to high-level decision makers. As one consultant tells STAT, “In a way, the FDA has always been a stepchild. It often gets trapped in bureaucracy.”
For instance, according to former commissioner Dr. David Kessler, there are 150 people between the FDA commissioner and the president — and “they all think they’re your boss.” Another former FDA leader mentioned he was never able to make it to the president — only the VP. The six former commissioners also agreed many decisions were made at levels above the FDA that went against the staff’s science-based recommendations.
The likelihood of the FDA becoming an independent entity is a little far-fetched at this point, and if anything, would be a long, long-term goal. It would require support from the new administration, as well as Congress, which might not warm to the idea because it already has some plans to reform agency functions. But even if this is currently a long-shot, there is something to be said about how an independent FDA could tie into a more accelerated approval of biosimilars. There need to be fewer barriers to biosimilar approval — and those barriers can certainly be people.
In the past few months of campaigning, Democratic candidate Hilary Clinton has emphasized her goal to make sure biosimilars without competitors receive accelerated approval and market release. Regardless of how the elections ultimately turn out, drug pricing has become a political platform and finding a solution has been charged to the highest levels of U.S. (and global) leadership. To put the FDA at, or closer to, the table where decisions are made would keep the purpose and benefits of biosimilars at the forefront of leaders’ minds and ensure these treatments remain a priority for the U.S.
Teva Welcomed Into PhRMA (7.15.16)
Great news reported today from PhRMA: After some hesitance from innovator members, PhRMA has voted to grant membership to Teva. There were concerns among current member organizations that the generic powerhouse’s record of challenging pharma patents went against PhRMA’s dedication to innovation. However, as we saw this week with the biosimilar AdComs (Amgen vs. AbbVie), innovators are going up against innovators to gain a portion of the biosimilar market. As I discussed in an article last week, we can no longer easily separate generics makers and innovators. Rather, we’re entering into a hybrid movement, where generics companies are getting a seat at the table to collaborate with innovators, while innovator companies investing in biosimilars are getting a view of patent challenges from the other, traditionally generics side. It does make me wonder what impact this movement could have on innovator patenting abilities. If innovators are both defending biologics from biosimilars and eliminating biologic patents to make room for their own biosimilars, it seems to me they could learn some new defensive tricks to strengthen patents protecting their reference drugs.
Just days after the company announced the FDA advisory committee’s recommendation to approve its adalimumab biosimilar, the company has made a deal with Daiichi Sankyo to commercialize nine biosimilars in Japan. Daiichi will be responsible for working with Japanese regulators and for marketing and distributing the biosimilars in Japan. Biosimilars included in this arrangement are adalimumab, bevacizumab, trastuzumab. Amgen is also currently developing biosimilars for rituximab, infliximab, cetuximab, and eculizumab. (There are still two undisclosed candidates in development.)
Daiichi Sankyo has been partnered up with Coherus since 2012 when the two companies struck a development and commercialization agreement for etanercept and rituximab. In fact, in January, the two companies announced successful Phase 3 results for CHS-0214 (Enbrel). The biosimilar is expected to enter Japan as early as 2017. Though Amgen’s decision to pair up with a company making a competitor to Enbrel has surprised a few people, Daiichi’s prominence in Japan should help Amgen gain solid footing in the country. Now that innovators are making biosimilars to challenge other biologics, entering a partnership with a competitor company just seems to be another example of the blurring lines in the biologics space.
FDA advisory committees voted unanimously to approve both Amgen’s Humira biosimilar ABP-501 and Sandoz’s Enbrel biosimilar GP-2015. This is great news for the U.S. biosimilar market and for patients. Though the meetings — especially Amgen’s — revealed pervasive concerns about extrapolation of the biosimilar into untested indications, the unanimous votes are encouraging. That said, however, there is still a great disconnect between the FDA and its advisory committees, which often had to ask clarifying questions about some of the basic aspects of the biosimilar pathway. But as one FDA speaker said, educating the panel was outside of their charge when it came to the recent meetings. It seems like it’s going to be the responsibility of the companies presenting candidates in AdComs to continue to educate each future panel.
These two biosimilars will undergo formal FDA review, with final votes occurring in the fall. However, there is no saying when Amgen’s Humira candidate will be able to hit the market after approval given Humira’s vast patent landscape. There have been some estimates that early 2018 will be the earliest possible release, while some expect it to be as AbbVie predicted — around 2022.
It’s been a topic of discussion amongst a number of experts in the industry about how we should be identifying and discussing biosimilars in public forums. For instance, The Wall Street Journal, among a number of other publications, have taken to identifying biosimilars as “knockoffs”— a word suggesting biosimilars are just not as good as the original.
I ended up getting into a lively discussion about the use of the word “knockoff” today on Twitter. The discussion ended up being the focus of an interesting feature on Endpoints (which also featured images of some of the tweets from those involved in the discussion, including yours truly.) For many editors, the use of “knockoff” comes down to avoiding excessive repetition of the word biosimilar in their work. Others look at the term as a way of signifying that biosimilars are the generic version of biologic drugs without calling them generics (which is also contentious). For instance, one response claimed the use of the term was just a way to protect an originator drug. At the end of the day, a drug is defined by its efficacy, not the name.
But when it comes to the battle between brand and biosimilar, there are already concerns about the efficacy of biosimilars. Consumers are more likely going to use and trust a brand medication when the alternative option is considered a “knockoff.”
According to pharmabiz.com, Indian drugmaker Cipla is making investments to launch a new manufacturing facility, which would be run by its subsidy, Cipla BioTech. Construction is expected to begin in early 2017, opening its doors in late 2018. The biosimilars produced in the facility will be used in South Africa primarily, with the potential for the products to be exported into the U.S., the EU, and Asia. Pharmabiz says South Africa is in dire need of cheaper biologics:
Currently about 1-in-50 patients in Africa have access to biologic medication. ‘We are striving to reduce this number to about 1-in-5 cancer patients through the production and supply of biosimilar medication at an affordable price,’ [says Paul Miller, CEO of subsidy company, Cipla Medpro].
The company hopes this launch will lead to the creation of a bio-cluster in Africa. As of July 2015, there have been no biosimilars registered in South Africa — even though a biosimilar guidance was finalized in 2014. According to GaBI, though there have been some biosimilar applications filed and reviewed, these applications were found non-compliant to biosimilar regulatory guidelines. For instance, candidates didn’t have nonclinical studies, or in some cases clinical studies were not performed or were insufficient to prove comparability Many submitted had been approved elsewhere via a non-biosimilars pathway. All of this information helps demonstrate the extent at which the country could benefit from biosimilars in the country.
In the FDA briefing documents released today, the agency announced that Amgen’s biosimilar data speaks to its similarity to Humira. The biosimilar is being submitted for the treatment of seven of Humira’s indications, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis. The briefing document states:
Amgen’s comparative analytical data for ABP 501 supports a demonstration that ABP 501 is highly similar to U.S.-licensed Humira, notwithstanding minor differences in clinically inactive components, and support a demonstration that there are no clinically meaningful differences…in terms of the safety, purity, and potency of the product to support…that ABP 501 is biosimilar to…Humira in the studied indications of rheumatoid arthritis and plaque psoriasis.
The Arthritis Advisory Committee will be meeting on Tuesday, July 12th to discuss approval of the biosimilar. Given the statement above, we’re likely to see a recommendation for approval. Similarly, because of the committee’s previous willingness to extrapolate, it’s likely the biosimilar will be approved for all indications listed. However, Humira is now up to 10 indications, so it will be interesting to see how the biosimilar label is handled. Granted, Humira has patent protection out the wazoo, so it’s anyone’s guess how long it will manage to keep biosimilar competition from the market.
Reuters reports that several pharmaceutical CEOs have created a task force to address any regulatory issues that should arise following Brexit. Industry members involved include GSK’s CEO Andrew Witty, AstraZeneca’s CEO Pascal Soriot, and life science minister George Freeman. The task force will be focusing on issues that arise related to intellectual property, trade, regulation, and employment. I’m glad to see two of pharma’s biggest British players stepping forward here. Though they’ve both claimed Brexit will not be enormously impactful on their financial standings, after a change such as this, there needs to be local parties involved in the establishment of future regulatory procedures — even should the country remain connected to the EMA.
Biosimilar makers are expressing concern about the latest pricing agreement in Ireland, The Irish Times reports. Though the new deal is supposed to save 775 Euros from the government’s 1.2 billion Euro budget, one lobby group is arguing that wording in the agreement will enable biologics prices to remain high. The lobby group, known as the Healthcare Enterprise Alliance, says the agreement includes “artificial pricing thresholds.” As Sandra Gannon wrote in a letter opposing the agreement:
We understand that consideration has been given to protecting a segment of the pharmaceutical sector whereby certain medicines – biologics – will be reimbursed at a price 30 percent less than current level, but only when competitor biosimilar medicines enter the market…[This clause] is nothing more than a biosimilars blocker...
According to Gannon, the 30 percent “blocking clause” would require companies to drop prices to levels “that are beyond commercial reality….The fallout will be twofold—firstly the fictional savings would not be realized, and secondly, biosimilars would be shut out of the market.”
The alliance is pushing for this rule to be removed from the bill. It also wants to see HSE prescribers required to prescribe biosimilars to patients in 40 percent of cases.
Ireland has been in the pharma news cycle lately because of Pfizer’s recent announcement that it will be expanding its biologics plant in Dublin. The Ireland plant currently manufactures Enbrel and the Prevnar vaccine. This agreement could be good news for Pfizer from an innovator standpoint, especially since the facility makes Enbrel. But it could stifle Pfizer’s interest in manufacturing/marketing biosimilars in the country. This is just another situation that seems to highlight the challenges facing Big Pharma today. After all, many of them are hybrid companies, invested in both reference products and biosimilars.
The country’s revised guidance has now limited companies’ abilities to waive comparative safety and efficacy studies. In the previous version of the guidance, this was permitted in “exceptional cases.” In the past few weeks, Roche has been spearheading challenges against Reliance Life Sciences and Hetero Drugs because of the labeling of their drugs as Avastin biosimilars. According to FiercePharma, these legal cases could have something to do with the widening of pharmacokinetic and pharmacodynamics criteria in the guidelines, along with the statement that confirmatory and efficacy studies are mandatory for mAbs.
Big news for biosimilar makers: The Federal Circuit has sided with the district court and ruled that the 180-day commercial market notice provision is required for all biosimilar makers. This means even if a company decides to engage in the patent dance and share its manufacturing information with the reference product maker, it will still be required to wait 180 days before launching its product.
As I discussed a few weeks ago, Sandoz has petitioned the Supreme Court about when this 6 months is allowed to begin—whether it must be after FDA approval or if it can be prior to the final FDA nod. The Supreme Court is currently referring to the Obama administration for its thoughts on the case. It’s unclear how this new decision will impact the Supreme Court’s decision to grant certiorari. Up to this point, chances were good that the case would appear before the Supreme Court. However, seeing Amgen’s triumph here, I’m not sure we can expect the Court to rule that the commercial marketing notice period can begin prior to approval—especially given the predictions of what will happen in the years ahead.
According to the Amgen v. Apotex appeal, though this decision gives biologics makers another 6 months of exclusivity, innovators will unlikely see longer periods of exclusivity in the future. As biosimilar makers target newer biologics, it becomes more likely they will be able to garner approval and grant notice of marketing prior to the brand drug reaching its 12-year anniversary. There’s also the chance the FDA could issue a license prior to the 11.5 year mark, which would take effective on the 12-year date.
A week has passed since the Brexit decision was made. Over the past week, the media has been inundated with speculation about how it will impact drug regulation and pharma companies. Obviously, it’s hard to say yet, though it seems the majority consensus is that the U.K. will work something out with the EMA in order to remain part of its regulatory pathway.
On a company level, big British companies like AstraZeneca (AZ) and GSK have said this decision will only minorly impact business. These two companies see 72 percent and 88 percent of their revenues garnered outside of the European markets. However, there is some speculation that U.K. over-cap stocks will become cheaper for U.S. and Japanese investors, opening up the question of whether this will attract potential acquisition partners for GSK and AZ. This could also be less likely due to the threat Brexit poses to regulatory affairs, market access, limited funding, in turn translating to a migration of talent from the U.K. According to BioSpace, one analyst expects biotech companies — especially Alexion, BioMarin, and Gilead — are the most likely to be affected by Brexit. (I’m unsure of this analyst’s reasoning here for BioMarin, in particular, because the company only sees 5 percent of its sales in the U.K.) According to Market Realist, there are actually a number of benefits biotech companies could realize from Brexit, including lower labor costs and interest payments (at least in the short term).
In an exclusive interview with RAPS, Emer Cooke, the head of international affairs at the EMA, said FDA has already observed inspections in upwards of eight countries in the EU. The goal is to complete observations of all member states by the end of 2017. Though there have been concerns in the past about sharing trade secret information, the FDA Safety and Innovation Act specifies that proprietary information can be shared between the FDA and other regulators.
These efforts are part of a larger movement toward harmonized global regulations. At the World Biosimilar Congress, the Pharmaceutical Inspection Co-Operation Scheme (PIC/S) was a topic of discussion for those looking to have their products approved in emerging markets. In recent weeks, the International Council on Harmonization (ICH) granted membership to its first biosimilar trade organizations (the IGBA). Joining these organizations is the International Coalition of Medicines Regulatory Authorities (ICMRA). The organization, which comprises regulators from 22 countries, aims to focus on supply chain, crisis management for global health outbreaks, and pharmacovigilance.
According to RAPS, the FDA and the various industry groups have completed negotiations over the second iteration of BsUFA. Together, the parties have agreed on the draft commitment letter, and the industry groups will now circulate the document amongst their members. This draft has yet to be made public, but several of the topics likely to be covered in the new commitment letter include: any enhancements made to the user fee structure as well as any alterations to the biosimilar review model. Two additional sticking points between the industry and FDA included: discussions over which party could determine face-to-face meetings with the FDA over a biosimilar application and the structure of the proposed FDA biosimilar review unit.
STAT reports that the Supreme Court declined to hear an appeal for a court case — a decision which has startled pharma firms like Eli Lilly, Novartis, and Pfizer. The appeal was from Sequenom, a California company which was forbidden a patent for its prenatal test because the methods used to analyze fetal DNA were already well-understood upon its invention (though the company was the first to apply the analysis to maternal plasma). This lower court decision was based on a previous Supreme Court case which argued that patents stemming from a natural process must more than simply state the law of nature while adding the words ‘apply it,’ reports STAT.
Many in the biotech industry are concerned this will lead to greater difficulties in patenting their products. If these fears are great enough, companies and investors may become less willing to fund expensive research projects. As STAT writes:
[Biotech patent lawyer Kevin Noonan] and others fear that the Supreme Court’s ruling was so broad that judges will be able to invalidate a slew of life science patents by picking apart the components of an invention to find the naturally occurring biological process that inspired it.
This specific case was not built around a biologic or biosimilar, specifically. The major concerns over this ruling seem focused on the future of diagnostic inventions or technology such as CRISPR-Cas9 gene editing — at least in this article. But the terms certainly sound broad enough to apply to a biologic medicine.
It’s come as a surprise to many — including to some of those who voted for Brexit — that the U.K. has voted to leave the EU. So far, England’s Prime Minister David Cameron has announced his resignation, and the European Medicines Agency (EMA) is facing relocation outside of London. Having read through several of the hundreds of news stories being churned out today about the decision and the questions Brexit leaves for the UK, the U.S., and the EU, a few key questions rise to the surface for pharma:
· What will come of the relationship between the EMA and MHRA?
· How much influence, if any, will the newly independent nation have should the U.K. decide to remain part of the EMA’s regulatory pathway?
· What would an EMA-MHRA partnership look like should relations between U.K. and EU be strained following Brexit?
· Since independence was one of the main goals, will the U.K. decide to form its own drug regulatory pathway?
· Will the U.K. forge a stronger relationship — or partnership — with the FDA, in essence creating what one publication has termed a “superpower” global regulatory body?
· Will the MHRA begin to resemble the agencies in Norway, Sweden, or Iceland?
· What will come of research and development funding from the EU?
· What impact will this have on biosimilar approvals and uptake in the nation?
· What impact will this have on approvals made by the EMA prior to Brexit? (This question becomes especially relevant should the country decide it wants to forge its own regulatory pathway.)
· How will this decision impact trade and the cost of imports — especially seeing as a number of drugs are outsourced for development in the EU?
· What impact will leaving the EU have on drug patent protection? Will some products be left without patent protection following the exit?
Inevitably, the market response to the decision has been severe and fear, shock, and concern are running high due to the novelty of the decision. The U.K. will have two years to negotiate the answers to some of these questions with the EU before being officially separated. The Director General of the newly minted British Biosimilars Association (BBA), Warwick Smith, has come forth arguing in favor of remaining part of the EMA’s single regulatory pathway in the hopes of eliminating excessive complexity and cost for drugmakers. I’d like to believe that the U.K. and EU will maintain the relationship with the EMA. However, as Tim deGavre, the chair of the BBA told me in an interview a few weeks ago, “The whole point [of Brexit] is that decisions should be made ‘in house.’” We’ll see how true this remains for pharma in the upcoming years.
Janice Shakowsky, a Democrat senator from Illinois, has introduced a bill called Price Relief, Innovation, and Competition for Essential Drugs Act. The bill is proposing shortening the biologics exclusivity period from 12 years to seven. The hope is that this will open the door to more biosimilars in the U.S. more quickly, in essence saving taxpayers upwards of $7 billion over the next decade. Shortening the period of exclusivity is not a new concept, having been one of the hang-ups in the Trans-Pacific Partnership agreements. President Obama has also included lowering this period to seven years in his budgets (though it’s never gotten much attention, for whatever reason). Hillary Clinton has also expressed her goal to shorten biologics exclusivity, as well as to prioritize biosimilars that do not have other competitors on the U.S. market.
So far, BIO has released a statement expressing its displeasure over the proposed bill, and PhRMA told STAT that it would harm R&D, slow innovation, and result in lost jobs. After the TPP negotiations and the fact the U.S. emerged from the TPP still carrying a 12-year exclusivity period, I’m less optimistic about this bill. There is also the very real possibility that, should this period be shortened, innovators would have more grounds to raise reference product prices. If those prices go up, you can bet that biosimilar prices will be higher and discounts will be smaller.
Roche’s CEO might be “sleeping better at night” because the recent successes have made the biosimilar threat less of a concern, but on the biosimilar side, one company is less than thrilled with Roche’s defense tactics. STAT writes that Russia’s Biocad has launched a lawsuit against Roche because its price cutting tactics in Russia are allegedly sabotaging Biocad’s biosimilars. STAT reports:
'While Roche and Genentech keep raising prices in the U.S., they engage in predatory pricing in Russia, where (they) sell such drugs at a loss — all to destroy (Biocad) and prevent it from entering the US market with cheaper biosimilars,’ the Russian company contended. For instance, Biocad claimed Roche sold 100 milligrams of Avastin to its exclusive distributor for 20 percent less than the officially declared price.
According to Biocad, these efforts violate anti-trust laws and are just another way for Roche to protect its cancer meds as they approach the patent cliff. This case, however, is pretty far-fetched. The goal of a biosimilar medicine is to spark competition and to lower drug prices for all similar products — reference and biosimilar alike. The only thing that seems unique here about this circumstance is the fact that a firm has actually decided to call a steep drop in reference product prices illegal. In the face of biosimilar competition, biologics makers are likely going to have to lower reference product pricing to compete — that’s just how this business works. That this would be a surprise to Biocad surprises me. If we start seeing more legal cases like this, we’re likely in for an even longer period of legal hassling over biosimilars.
A peer-reviewed publication by Pfizer’s Reginald Ewesuedo argues against the use of “phase” when describing biosimilar clinical trials. Rather than rely on the term “phase,” as is used for novel drug trials, Ewesuedo suggests that “step” would be much more fitting for biosimilar trials. He writes:
It is reasonable to suggest that [the Phase 1 study] should only be referred to as ‘Comparative Clinical PK study’. Such a description conveys to the reader this is a PK study that is ‘not’ akin to what is typically expected for a Phase 1 study, instead there is a known PK profile being elucidated for comparison in the study. The next study, if not an efficacy study, would typically evaluate the PD property(ies) of the biosimilar. Such a study when referred to as ‘Comparative Clinical Pharmacodynamics Study’ should characterize a step in the development scheme, where PD can be integrated into the process. The ‘efficacy’ study should be referred to as the ‘Comparative Clinical Efficacy Study.’ This study is intended to demonstrate similarity using a typical clinical activity and/or endpoint for both the biosimilar and reference product.
This was an interesting read, providing a decent suggestion for what is proving to be a big hang-up for physicians. Indeed, physicians need to be taught that the data/clinical structure with which they’ve used to evaluate new drugs is different for biosimilars. If biosimilars are going to be named differently than typical generics, and if doctors will need to learn to embrace different data, it makes sense to change the typical clinical terminology for biosimilars to more closely embrace the differences in the clinical process for these drugs.
Mitsubishi Gas Chemical and Nippon Kayaku have partnered up to make mAbs in Niigata, Japan within the next two years, says BioPharma-Reporter. The joint venture, named Cultivecs, aims to develop mAbs, biosimilars, and to be a contract manufacturer for these kinds of products. Nippon Kayuka has experience working with biosimilars, having established a partnership with Celltrion on its infliximab biosimilar (approved in Japan in 2014). The partners are now at work on a trastuzumab biosimilar. Representatives from the companies have said there is great need for local biologic development in Japan.
Japan is highly dependent on import of biologics, which is estimated to exceed $5 billion every year. Made-in-Japan biologics of high quality with stable supply security system are highly required.
It seems like a lot of countries are pushing to eliminate their reliance on imports these days. I’m keeping my eyes on this partnership, as well as Japan, because of the fact local players have been partnering up with Korean companies. The fact that this partnership is with a company that has had success with Celltrion also bodes well for both the new JV and, hopefully, Japan’s contribution to the biosimilar market.
Pfizer is shelling out $200 million to build a biologics manufacturing plant in Andover, MA, FiercePharma reports.
The 5-story facility will have 5 independent manufacturing suites with flexible design, using single-use bioreactors and disposable process technologies. The new facility is expected to be operational by January 2019.
It hasn’t been said explicitly, but when I hear the words “Pfizer” and “new biologics manufacturing facility”, I can’t help but think “biosimilars.”
While this article doesn’t contain any earth-shattering/new information, I give props to the blue latitude health blogger for the creativity of relating the biologic vs. biosimilar decision with Brexit. The blog says: To understand the factors influencing the uptake of biosimilars you could apply the same principles as you would to navigating the complexities of Britain exiting the EU (Brexit).
The Supreme Court has turned to the Obama administration to gain more input into when a biosimilar should be launched, STAT reports. Following the continuing Amgen vs. Sandoz saga, the biggest question remaining is when must the biosimilar maker provide the brand manufacturer with the 180-day notice of intent to sell a biosimilar? Sandoz has petitioned the Supreme Court to decide if the 180-day notice can be provided prior to FDA approval, or if it must remain after the final nod from the FDA, as originally determined by a federal court. The decision could give the brand company another six months to stir up additional patent disputes, in turn slowing the arrival of the biosimilar to market. As it stands now, the Supreme Court is still trying to determine whether to take the contentious case. Goodwin Proctor’s William Jay says,
The chances that Sandoz will persuade the court to take the case have just gone up. The executive branch has to make a choice: Does it think the best outcome for public policy is to make people wait 180 days or not for a lower-cost medicine?
It all boils down to the question that seems to be central in the emerging biosimilar market: will the powers that be side with biosimilar makers or branded makers? So far the FDA seems to be trying to cater to both parties. For instance, take naming and labeling: while branded makers got their wish for differentiated names, biosimilar makers "won" the labeling decision (at least so far). The draft guidance does not call for biosimilar labels to contain comparative data to the reference product. Only a statement designating the treatment a biosimilar to a branded drug is required (a move which attempts to cater to branded makers’ wishes.) My bet is if the Supreme Court takes the case, there will be some sort of halfway point established. Companies that have participated in the patent dance are currently arguing they should be exempt from the 180-day notice. I could see the Supreme Court taking a similar stance.
The FDA caused a stir a few weeks ago when it released a document specifying that biosimilar makers would be permitted to submit 10 suggested suffixes for their biosimilars. These suggestions were also allowed to be ranked in terms of the drugmaker’s preference. Though these 10 suffix proposals were supposed to be meaningless as specified in the draft guidance, many, including myself, were questioning just how random or meaningless these proposed suffixes would end up being.
However, it seems this hullabaloo was for naught. The FDA has now retracted this document, claiming its publication in The Federal Register was an “administrative error.” As RAPS reports, the FDA’s Leah Christl claims the agency’s allowance of 10 suggestions was an arbitrary number and that it was not a gateway towards more meaningful suffixes. Regardless, publication of a document in the Federal Register is a pretty big “administrative error” to make. The whole retraction seems questionable to me — especially since it took 20 days to be withdrawn. (And, given media response following the publication, I can't imagine the FDA was in the dark about the document being published in the first place.) Begs the question if it wasn’t withdrawn because so many began speculating about whether the agency was loosening its stance on just how meaningless the suffix needed to be.
It’s looking like EPIRUS might have some competition from Amgen, which has launched trials for a Soliris biosimilar (ABP 959). The study was first announced in April in the Australia New Zealand Clinical Trial Registry (ANZCTR), BioPharma-Reporter says. The drug is a great candidate for a biosimilar version, considering it cost NICE 340,200 pounds for the initial/maintenance treatment in the first year of treatment. (It costs 327,000 pounds for the recommended maintenance dose for a year of treatment.) Amgen has announced little else about the development of the biosimilar.
In the reports surfacing, I’ve seen a number of reports highlighting EPIRUS’ work on the Soliris biosimilar. Some have even said that Amgen and EPIRUS are the only two working on a contender for this molecule. But Harvest Moon also has a candidate in its third wave of biosimilars anticipated between 2018 and 2026. The company is currently seeking partners, but is planning an EU, U.S. submission in the first quarter of 2018.
Biosimilars appear to be living up to their purpose: a recent IMS report has revealed that biosimilars are saving money — even if the percentage of their uptake is low. The report tracked savings generated from epoteins (EPOs), granulocyte-colony stimulating factor (G-CSF), human growth hormone (HGH), and anti-tumor necrosis factor (anti-TNF) drugs. According to the report:
In countries which used to have low usage/availability in the classes, the price reductions seem to have a significant impact on the increased access. For the 4 classes we can see the same pattern; high savings can be achieved even if biosimilar uptake is low.
For some of the figures from the report and the link to the IMS report, check out the RAPS story.
The International Generic and Biosimilars Trade Organization (IGBA) has been granted membership to the International Council on Harmonization (ICH). This is the first time a generics/biosimilar trade group has been accepted as an assembly member to the ICH. The IGBA — previously known as the International Generic Pharmaceutical Alliance, or IGPA — was previously denied membership to the ICH’s steering committee in 2014. However, now as an assembly member, the IGBA will be able to contribute to the development of a harmonized approach to generic/biosimilar drug development.
Sandoz has ambitious plans to get 11 biosimilars filed for approval in the EU and the U.S. by 2020. In order to do this, the company will need to continue to fine-tune its manufacturing capabilities, says BioPharma-Reporter. The company recently pushed 150 million Euros into expanding its Schaftenau, Austria manufacturing site. This is a small amount, however, compared to what the company intends to spend overall. As BioPharma-Reporter writes:
This represents just 15 percent of what Novartis says it is spending to boost capacity for both innovative biologics and biosimilars in Austria. [Carol Lynch, global head of biopharmaceuticals, Sandoz] says this heavy internal biomanufacturing investment is intended to bring “all of our biologics manufacturing under one roof, figuratively” to ensure the firm has the capacity required…[Lynch says,] "Here in Austria between this site and the one…in Kudel, between 2010 and the end of the decade, $1 billion will have been invested to support the expansion of manufacturing capacity...You have to financially commit for the long-term."
Lynch also specified that Sandoz hopes to keep all manufacturing in-house in the future, rather than turning to CMOs.
It’s certainly ambitious, but Sandoz would be on my short list of companies that could accomplish it.
The U.S. could see a recommendation for approval of its third biosimilar, Sandoz’s etanercept (Enbrel). The Arthritis Advisory Committee will be reviewing the biosimilar for approval to treat rheumatoid arthritis, juvenile idiopathic arthritis (ages 2+), psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis.
According to BioPharma-Reporter, a topic of conversation at this week’s BIO conference was the lack of production capacity in the biopharma sector. This is especially true for small and midsize companies. As Steve Lam of Patheon says:
Because of the new technologies that are coming in, in terms of single use which has led to smaller reactors, there are opportunities, but contract manufacturers are going to have to be creative.
The article goes on to outline a couple of different models Patheon (and other CDMOs) are employing. Certainly worth a look to get a refresher on the shape the CDMO market is taking today — especially given the varying growth of the biosimilar market globally.
The National Law Review reviewed 111 Inter Partes Reviews (IPRs) filed by generic drug companies. IPRs have taken center stage as a big patent concern for patent holders in the pharma industry over the past few years. For instance, BIO’s Hans Sauer tells Life Sciences Intellectual Property Review, There are different courts which have different sets of rules, and we find that troubling. On the biosimilar side of things, we recently saw Coherus’ IPR of two of Humira’s patents passed on to court. According to the results of the National Law Review’s survey,
We found an institution rate of 67 percent, which is not significantly different from the general rate of institution across all technologies, showing that generic companies are achieving a comparable institution rate. While a greater number of these IPRs resulted in a finding of all instituted claims being patentable in final written decisions (FWDs) compared to IPRs across all technologies, the sample size of FWDs is so small (9 IPRs) that it may be premature to read too much into this.
It’s impossible to know the extent to which this type of patent challenge will impact the biosimilar market. But I’ve continued to keep my eyes on the process, especially since there are a number of biosimilar companies exploring this method to get more quickly through the litigation phase holding back the market. There are several efforts underway to reshape or limit the use of the IPRs by generics/biosimilar companies. So to say it’s “premature to read too much into the success or failure rates of IPRs” for generics/biosimilar companies is spot on.
Last fall, Regulatory Affairs Professionals Society (RAPS) reported that Hilary Clinton would push for a more biosimilar-friendly environment should she be elected to office:
[In September 2015], Clinton unveiled a plan that would decrease the market exclusivity for biologics from 12 years to seven years…Under the proposal to lower the exclusivity period for biologics, Clinton also calls on the FDA to ‘give prioritized, expedited review to biosimilar applications that only have one or two competitors in the marketplace.’
This all sounds great. But do we remember the Trans-Pacific Partnership (TPP) agreements?
Hans Sauer, deputy counsel of Intellectual Property for BIO, was featured in a Life Sciences Intellectual Property Review article, discussing some of the IP challenges facing the Biopharma industry.
With the clarification of the ‘patent dance’ rules following the Amgen v Sandoz case on biosimilars, Sauer says this area is still a ‘work in progress. There is uncertainty, but that uncertainty is in no way crippling or paralyzing anyone,’ says Sauer. ‘All the companies I speak to look forward to the prospect of the patent dance in a very rational way. They are very calm and prepared and they know it’s going to come out in one way or another. Even though the patent dance may not be unfolding how people would have expected, I think currently it looks as though the courts are nonetheless trying to achieve the overall objective of early notice and opportunity to resolve disputes before products have been launched.’
Sauer makes some great points here — especially his emphasis on how companies are approaching the patent dance procedure. Because of the frequency of patent litigation —especially standing before the biosimilar market’s growth — it seems like it’s a much more unsettling process than Sauer has made it out to be here. Sauer participated in an interview about the IPR process for Life Science Leader magazine a few months ago. It’s a good read if you’re interested in the impact the Inter Partes Review process will have on the future of drug development.
CEO of Pfizer, Ian Read, like many others in this industry, doesn’t expect competition from biosimilars to begin eroding sales of the company’s biologics, including Enbrel, immediately. Sitting at the helm of a company that will be putting forth both reference drugs and biosimilars, Read says:
It is an opportunity for biosimilars to capture the new patients, and as time goes by, also begin to get a growing share of patients who will get switched over. But it won’t happen immediately. I think the biosimilars market will look more like the sterile injectable market in terms of pricing and erosion.
Merck and J&J might have some different ideas on how price erosion plays out.
According to FiercePharma, Novartis is keeping Asian biosimilar players in its sights to “complement” Sandoz’s biosimilar pipeline. And apparently, according to Fierce: In the past [reports have] surfaced that CEO and founder [of Celltrion]Seo Jung-jin wants to sell his near 30 percent stake.
If the biosimilar market performs in any way like the generics market overtime, we should expect consolidation among the players. Given Celltrion’s expertise commercializing its infliximab biosimilar, and Novartis’ strength at marketing, the two could make for an interesting match.
CBER, WHO Team Up To Boost Biologics Access (6.2.16)
Regulatory Affairs Professionals Society (RAPS) reports the FDA’s Center for Biologics Evaluation and Research (CBER) has strengthened its relationship with WHO to strengthen global regulatory systems and standards to boost access to safer biologics. CBER will be providing upwards of $2 million this year and possibly every year until 2020. RAPS says:
The funds will help support assessments and analyses, particularly on vaccine regulatory capabilities and pharmacovigilance, as well as the development of an institutional plan to enhance regulatory performance in low- and middle-income countries. CBER is also looking to strengthen regulatory systems at the national and regional levels around good manufacturing, clinical, and laboratory practices; monitoring and evaluation of product quality; lot release; inspection and surveillance of products throughout the supply chain; pharmacovigilance systems building and analyses; risk assessment and analysis and management.
These efforts can only benefit biosimilar development and increase access in less developed nations.
Medical Marketing & Media published results from a survey determining the willingness of global and U.S. physicians to prescribe biosimilars. The survey posed the question” Will U.S. physicians prescribe biosimilars? According to the survey of 3,478 global physicians (1,789 from the U.S.), 48 percent of U.S. doctors expect they’ll need more information prior to prescribing biosimilars. However, interestingly, 44 percent of U.S. docs claimed they would prescribe biosimilars, while only 8 percent said they would not. But the real meat of this article is the pblication of a U.S. rheumatologist’s impassioned statement against using biosimilars. Here is an excerpt:
Approving such a totally new chemical compound to be marketed to treat potentially millions of patients with a half dozen different diagnoses … without thorough testing? Is political idiocy … Not medical science. Nobody knows if they will be ‘safe.’ Nobody knows if they will be ‘effective.’ Certainly not the FDA or any of the European drug-regulatory agencies… The FDA is proposing taking very promising compounds and turning them into treatments one step away from snake oil (which was also marketed without appropriate testing).
This all seems too extreme to represent the majority of physicians in the U.S. But it serves as a good reminder what patient groups, physicians’ associations, and manufacturers are facing when it comes to educating stakeholders.
Last week, I discussed Roche’s work on Gazyva and the threat it poses for biosimilar versions of rituximab. This week, Roche announced it had won approval from the EU for its subcutaneous version of MabThera to treat chronic lymphocytic leukemia (CLL). Roche’s Dr. Ulrike Engels-Lange told BioPharma-Reporter:
As MabThera SC can be given under the skin, it cuts delivery to approximately 7 minutes compared with 2.5 hours for the intravenous formulation, without compromising MabThera’s proven efficacy and safety.
An interesting development to be aware of here.
According to Reuters, Roche and Novartis — though both Swiss companies — are pursuing different strategies in the face of the impending biosimilar tidal wave. Novartis’ Sandoz is a leader in the biosimilar sphere, and currently has a rituximab biosimilar up for review in the EU. But for Roche, the biobetter (Gazyva) and innovator strategy has been the path the company is choosing to follow. As such, Novartis is considering selling its $14 billion stake in Roche. Though Roche has yet to comment on Novartis’ plans, Joe Jimenez had lots of interesting things to say. Here are some of the highlights:
Joe Jimenez said last week… he would unleash ‘one of the best and most-potent oncology sales and medical forces’ to peddle rituximab, Rituxan's generic name, in Europe as early as next year.
I’ve written before the company is a master at marketing its biosimilars. I’d hold this company at its word.
As Roche musters new data on its next-generation drugs, Jimenez last week fired off a warning: Biosimilar copies will likely sell at discounts of as high as 75 percent versus the original product, far deeper than Novartis originally anticipated.
If this is legitimately true, I can’t believe this warning didn’t make headlines last week. That estimation would be higher than Norway’s jaw-dropping 69 percent infliximab discount. And most big industry experts expect this discount will be much too high to be feasible in the U.S.
Jimenez said the aggressive legal strategies of drug originators to delay would-be copies have replaced government approval as the biggest stumbling block to speedy U.S. biosimilar introductions. ‘You're seeing less regulatory time, more blocking,’ he said. ‘Eventually, as the legal battles are won, you're going to see a good business in the U.S. with biosimilars.’
While many of the frustrations I hear stem from delays in FDA guidance and the formation of the regulatory pathway, Jimenez reminds us of this good point. I’ve heard the U.S. referred to as “trigger-happy” when it comes to litigation. So far, I’d say considering the litigation surrounding current biosimilar contenders, this is an accurate statement.
This is an interesting article overall — I’d suggest reading the whole thing through.
Last week, Samsung filed its infliximab biosimilar with the FDA for approval. Should it get the agency’s nod, it will enter the market as the first infliximab competitor in the states to Celltrion’s recently approved Inflectra. As such, these two companies are going to be the first two companies to battle over biosimilar market share and pricing in the U.S. But now, they’re both also making improvements to their manufacturing structures to bolster capacity. The latest news on this front comes from Celltrion.
According to BioPharma-Reporter, Celltrion is investing $275 million to boost capacity at its Incheon site (currently containing two cell manufacturing plants) from 140,000 L to 310,000 L by 2021. A third plant that will be built in the upcoming years will now house 120,000 L, as opposed to the 90,000 L originally planned.
But Celltrion’s not alone in its efforts to bolster capacity: Samsung Biologics announced just a few months ago it would be adding a third plant to its Songdo site, bringing cell culture capacity to 360,000 L by 2018.
It’s becoming clear we have two Korean biosimilar powerhouses on our hands here. I am particularly curious to see how the two infliximab candidates compete in the U.S. market. Celltrion has some direct advantages. For one, the company structured the deal with Orion Pharma in Norway, which led to the jaw-dropping 69 percent discount and increased market uptake. Similarly, the company has years of experience with infliximab in Europe. Of course, nothing can be predicted about which company will come out on top here in the U.S. should Samsung's biosimilar be approved. But for now, I'm seeing some interesting competitive stirrings between these two big players moving forward.
According to The Pharma Letter, Parliament is pushing for the European Commission to implement a Supplementary Protection Certificate (SPC) manufacturing waiver by 2019. If this is carried out, the EU will gain additional jobs and stimulate the growth of the European generic and biosimilar industries. As The Letter writes:
The export of generic and biosimilar medicines to unprotected markets during the SPC period will stimulate investment in Europe, support the creation of highly skilled jobs, and increase access to high quality medicines in third countries, without changing the equilibrium between the originator and the generic and biosimilar medicines industries in the EU.
Gazyva, Genentech’s new, in-progress lymphoma drug, released some interim Phase 3 studies that suggest Rituxan (rituximab) might be facing a newer, shinier competitor — just as biosimilar competition is closing in on the market. As Seeking Alpha describes, the Phase 3 GALLIUM study so far has demonstrated that Gazyva has significantly reduced the risk of disease progression or death compared to Rituxan. The trial is comparing Gazyva plus chemo then Gazyva alone to Rituxan plus chemo then Rituxan alone in treatment naïve follicular lymphoma patients.
Genentech’s work on this candidate is one of the forefront and frequently mentioned “biobetter” efforts today. There really is no guarantee that it will overtake the use of rituximab biosimilars (though there has only been one filed thus far for approval in the EU). The real concern here would be the drug’s significant performance over that of Rituxan. Payers are increasingly demanding comparative data that demonstrates why a drug is going to be better than the current standard of care. Genentech might’ve just found that key to payer preference. But it’s also going to come down to price.
Pure-play Coherus BioSciences announced in a press release today that the company has been awarded three patents for its formulation of its Phase 3 Humira biosimilar molecule, CHS-1420.
The United States Patent and Trademark Office (USPTO) issued to Coherus U.S. Patents 9,340,611; 9,340,612 and 9,346,880. These patents generally concern formulations of adalimumab, the active biological ingredient in Coherus’ Humira biosimilar, CHS-1420, currently in Phase 3. The formulations described in these patents achieve stability without need for polyols or surfactants.
Coherus is really setting the bar high in the IP realms these days. This news follows the USPTO’s decision to uphold the company’s Inter Partes Review (IPR) challenge of three of Humira’s patents last week. Talk about a competitive strategy here. Paul Calvo submitted a great article about patenting biosimilars a few months ago. One of the big pluses of this move is that Coherus has effectively established another way its biosimilar can compete against other biosimilar makers in the market beyond price.
Medical Marketing and Media posted an interesting article that highlighted the various ways biosimilar uptake is being approached by members of Big Pharma, generics companies, trade groups, and Prescription Benefits Managers (PBMs). Perhaps the most interesting part of the story was in the section covering generics manufacturer perspectives. As John Clarkson, SVP, management supervisor at H4B Chelsea, points out, Sandoz’s marketing tactics make the company a pioneer in the biosimilar space. As he says:
It seems they were able to differentiate a product that was developed to be a clinical equivalent of something else. Standing out when a product isn't meant to be different is a pretty significant hurdle to clear.
I’ve heard this as well, about Sandoz. In a recent interview, Plantform’s CEO, Don Stewart, pointed out that even though Sandoz’s human growth hormone biosimilar was not the first biosimilar on the market, it ended up being the most successful because of the company’s marketing strategy. Overall, I’d give this article a read-through, as it includes interviews about Merck’s strategies for education, The Biosimilars Forum’s work in the market thus far, and other trinkets of information that might catch your eye. (For me, one such trinket of information, however horrifying, was that people are out there referring to biosimilars as “bathtub biosimilars.” And here I thought calling biosimilars “knock-offs” was a low-blow.)
In his column “China’s War On Big Pharma Exposes The Mirage Of Market Access” in Forbes, Douglas Bulloch describes how the Chinese economy is becoming less welcoming to Big Pharma. For one, the economy is shifting to resemble that of an Indian model, rather than a Western model, as originally expected. He writes:
A central government initiative – taking example from India – to simply demand price reductions on key drugs… comes on top of last year’s decision to put “generics” and “branded products” on the same price control regime, meaning branded products are simply not allowed to benefit from the premiums generated by lack of consumer trust in generics. Until now, market entry has always been a key criteria for investment in China, fueled by the expectation that the Chinese market would eventually develop and become more normal, but it looks increasingly likely that China is going the way of India, and this is bad news for all.
There’s been a lot of emphasis placed on China’s attempts to draw Big Pharma into the country in the past few years. The CFDA has also set about to make the country more regulatory-friendly so drugs can be approved and put in patients’ hands more quickly after years of backlogs. Indeed, the market was shaping up to be innovator-friendly, and not just a generics hub. But if the country is adopting some of the same practices as India (check out the link in the quoted portion above), I’m curious about the impact this could have on the growth/uptake of biosimilars. Similarly, if there is less interest from Big Pharma organizations (some of which are also launching biosimilar businesses), does this open up the country to smaller international biosimilar manufacturers? This could be a sweet opportunity for some of these smaller companies, given the rising use of the mAb market in the country.
Single-use has been on the industry’s mind for a while now, but it’s come up in two separate discussions this week. In an interview with Pharmaceutical Processing (PharmaPro), Michael Wyand, CTO of EPIRUS Biopharmaceuticals, argues in favor of single-use for increasing the development of biosimilars. He tells PharmaPro:
Single-use technologies are advantageous because they give us the ability to control parts of the manufacturing process. For example, if you were to manufacture a drug in one manufacturing plant and then move it to a second plant, you can use the same single-use technology in both plants. This minimizes changes batch to batch and allows for a greater chance of consistency in the manufacturing process.
Capacity is going to be a big challenge for biosimilar firms looking to tackle the global market for biosimilars. Stainless steel has been great for creating large batches of blockbusters, and perhaps will still be the answer for those making biosimilars for the big blockbuster biologics (Humira, Remicade, etc.) But, as an interview in BioPharma-Reporter today also discusses, the orphan drug rush means that biologics (and therefore, in many cases, future biosimilars) are targeting smaller groups of people. This has hit closer to home following EPIRUS’ recent leap into the orphan drug biosimilar space.
For companies expanding their manufacturing bases to span the markets, single-use would provide a more consistent manufacturing process for biosimilars — especially important for biosimilars given the variations that can happen from batch to batch. We’re also seeing, especially in the Latin American markets, the growth of international partnerships with the end goal of creating local manufacturing facilities for biosimilars. For international companies, turning to single-use would ensure the consistency of the product from country to country.
In an interview with Business Insurance, Dr. Steve Miller, the CMO of Express Scripts, says that Basaglar, the first biosimilar for Lantus, is coming out this year. And, luckily for patients and biosimilar makers, Lantus is the PBM’s preferred treatment, meaning it'll be a lot easier for ... our plans to switch people to the biosimilar for Lantus when it comes to the marketplace.
He also highlights what many of us already know — that beyond diabetes drugs, the anti-inflammatory drugs are the highest drivers of prescription drug spending. He says:
Indication-based pricing has been working well for us as an experiment for cancer treatments. And so we’re also looking at the possibility of expanding indication-based pricing into the anti-inflammatories, probably for 2017.
It’s also important to realize that what happened in the Hep C space between Gilead and AbbVie is likely going to have to happen within the biosimilar industry. For instance, he states:
We don't want our competitors to know what the prices are. If we had to let the pharmaceutical companies know the price we were being offered from another pharmaceutical company for hepatitis C, would we have been successful to create a price war there? The answer is probably not. Gilead (Sciences Inc.) would not have gone any lower (on its price for hepatitis C treatments) than they had to if they knew what the AbbVie (Inc.) price was.
This interview continues to remind the industry that the PBMs have a great amount of control here, both over what gets distributed to patients and at what price. What exciting to hear is that biosimilar insulin is going to be the preferred treatment for Lantus moving forward, especially since this space is ripe with biobetters and evergreening. Take for instance the news from diabetes heavy-hitter Novo Nordisk this week that an FDA panel has recommended approval for its new diabetes drug. IDegLira is a combination of Tresiba (insulin degludec) and Victoza (liraglutide). Similarly, following in its footsteps, Sanofi’s iGlarLixi (combo of lixisenatide and Lantus) went before the FDA committee and received a positive recommendation. This is, perhaps, a bit concerning for biosimilar Lantus. But I’m going to return to Express Scripts decision to pick up AbbVie’s Hep C drug over Sovaldi, despite the fact Viekira Pak was a bit more complicated to take (two separate pills) — it’s all going to come down to price.
According to BioPharma-Reporter, Mundipharma has released new data from its two-year study of Remsima, proving the biosimilar is as effective and well-tolerated by rheumatoid arthritis patients as Remicade. Mundipharma is responsible for distributing Remsima in Germany, Italy, U.K., Netherlands, Belgium, and Luxemborg. A Mundipharma spokeswoman says this study aims to inform the healthcare community of the emerging long term data and provide reassurance that efficacy is maintained in the longer term.
I wasn’t particularly surprised to hear this news. As experience has shown in Europe, reports of major adverse effects from taking biosimilars have been few and far between. In fact, according to Norwegian Medicines Agency’s Steinar Madsen, there have been only seven or so patients that have reported adverse events while taking biosimilar infliximab, and the uptake/switching in that country has been huge.
Extrapolation: An Ongoing Debate In Brazil (5.18.16)
Brazilian publication OncoNews (translation necessary) discusses the evolving regulatory market for biosimilars in Brazil. In March, The National Health Surveillance Agency (ANVISA) denied the approval of Celltrion’s Herceptin biosimilar. Though this article did not delve into the reasons behind ANVISA’s rejection of this biosimilar, it demonstrates that, despite the country’s interest in producing biosimilars, there is still a great deal of caution about these treatments. In fact, the decision to approve Celltrion’s infliximab biosimilar for all indications as Remicade went against the established law. As OncoNews writes (translated):
According to the RDC 55, 2010, to approve a drug with extrapolation it needs to check data with the most sensitive target population for this indication, both the effectiveness point of view, the immune reaction. And this was not done [in the case of Celltrion’s infliximab biosimilar.]
Not only is extrapolation a concern, but so are the side effects that can come from treatment with a biologic — and, in turn, the ever-so-slightly different biosimilar version. These are the questions causing controversy everywhere — most recently in the U.S. When ANVISA approved infliximab, there was previous evidence from the EU of the drug’s ability to be extrapolated. But, similar to many other countries with biosimilars in the regulatory pipeline, the primary question the article poses is whether Brazil will be ready for the arrival of second-generation biosimilars?
A post by Nigel Rulewski, VP global strategic drug development and head of Quintiles Global Biosimilars unit, discusses what characteristics are ideal for biosimilar Phase 1 sites. He also discusses some of the aspects companies should consider when determining which market will be best for the development of their biosimilar. As Rulewski writes:
Patient recruitment can be accelerated by choosing the countries or markets that have the greatest unmet need for the biosimilar. However the sites in these markets may have little experience running biosimilar clinical trials, and/or they may lack the basic infrastructure and talent pool to effectively manage these trials. On the other hand, companies can accelerate speed-to-market by selecting markets in which regulatory agencies are willing to work with companies to bring biosimilars into market earlier, most often in markets where governments are incentivized to reduce healthcare costs. However, sites in these markets may be less interested in participating in biosimilar development, because it does not involve novel research and there will likely be more competition for patients.
In past conversations with experts in the clinical space, I’ve heard similar concerns about holding trials at sites in more regulated markets, such as the U.S. In particular, I’ve heard novel research holds a lot more allure than biosimilars, and as such, can make it more difficult for sponsors to find investigators and sites that are willing or able to participate.
Coherus announced the U.S. Patent and Trademark Office (PTO) will review a petition against several patents safeguarding Humira. Coherus currently has a Humira biosimilar in Phase 3 clinical trials. There have been an increasing number of biosimilar and generics makers turning to the Inter Partes Review (IPR) process, which promises a more efficient and cost-effective review process of patent claims. AbbVie’s only comment to Reuters was that it plans to “rigorously defend” its patents, which are rumored to protect the biologic from competition until 2022.
According to Bloomberg, Coherus believes the patent is invalid because the dosage regimen it covers was a routine optimization of the therapy that was known by researchers. The company is also filing the same argument for two other patents. In addition, a third patent protecting the drug’s formulation was just challenged last week. AbbVie says these claims are weak because they are merely rehashing the same arguments thoroughly considered by the examiner during the application process. However, according to the three patent judges, there is a reasonable likelihood Coherus could prevail.
This is a big win for the biosimilar industry, especially given Amgen’s big IPR loss to AbbVie a few months ago. Between this big loss, and several biosimilar maker IPRs that have been turned away, it was unclear how the IPR process would work for biosimilar challengers. This is far from a black and white procedure, and there will likely be more losses before more wins. Similarly, there’s no guarantee the review now set to take place within the next year will come out in Coherus’ favor. But for now, I think this development should be reassuring to biosimilar makers looking to challenge reference drug patents via IPR.
According to BioPlan Associates’ Eric Langer, there is little consensus over the metrics of how successful the biosimilar market will be. In a column for Genetic Engineering & Biotechnology News (GEN), Langer argues this is because there are very few biopharma and biosimilar information resources in existence. Based off a chart highlighting the primary reference drug targets, Langer offers an estimation of the size of the biosimilar market:
BioPlan Associates expects an eventual average of eight or more biosimilars entering the U.S. and other major markets for each candidate reference product. (Reference products include >100 marketed recombinant proteins/monoclonal antibodies). Soon enough, biosimilars will considerably outnumber innovative and other reference biopharmaceutical products.
Eight is a good guess, considering there are upwards of twelve first wave candidates in development. The space is also facing a large amount of interest, according to a newly released ISR report. While last year, 54 percent of respondents claimed their company had no plans to sell biosimilars, this year, that percentage shrunk to only 36 percent of respondents. So, no surprise here, biosimilars are the hot new commodity. That said however, eight seems safe given the turnover that will inevitably happen in the space. (Take EPIRUS’ recent decision, for example).
FiercePharma reports that UPS is collaborating with robotics company Zipline and Gavi, the Vaccine Alliance, to deliver blood to western Rwanda using unmanned aerial vehicles (UAVs). The Rwandan government is hoping to use these drones to make 150 deliveries a day from a central location to 21 blood transfusion facilities in the country's mountainous Western region. As Fierce writes, should this trial be a success, this project could be extended to vaccines, AIDs treatments, malaria, and tuberculosis.
This could be an interesting solution in nations where maintaining the cold chain poses issues for biologics and biosimilars.
Last month in a controversial ruling, the Delhi High Court ruled that biosimilar products being produced by Biocon and Mylan needed to change the labeling and packaging of their Herceptin biosimilar. Now, Roche is suing the Delhi High Court and Hetero Drugs over the approval process of Hetero’s Avastin biosimilar, The Economic Times reports. The company argues the attention is simply to ensure the safety of patients. Given quality concerns in India in recent years, there could be some validity to these concerns. But given the continuing increase in litigation over the past few months from the firm, Roche’s moves are starting to look more like a defense mechanism.
Sanofi’s Elias Zerhouni has continued to push for a harmonized regulatory structure to improve access to new medicines, Reuters reports. Along with the FDA’s former head Margaret Hamburg, Zerhouni is urging governments and top officials to harmonize the “mosaic of regulations” in different countries. Even though there has been some improvement, there are still many examples of new drugs being held back from patients because of different requirements from country to country. Take for instance, Sanofi’s new dengue fever vaccine, which is being held from the Chinese and Indian markets because of demands for separate clinical trials.
Nearly 40 percent of drugs used by Americans, for example, are made elsewhere and 80 percent of the active pharmaceutical ingredients in them are manufactured overseas. The current system is simply at odds with the nature of the supply chain, said Zerhouni…The regulation of drugs can either grease the wheels of progress or throw a wrench in the works, Hamburg and Zerhouni concluded. We believe that harmonized drug regulation has the potential to be the unsung hero in driving improved health along with global economic and social development.
I’ve always enjoyed hearing Zerhouni’s discussions on this topic. Though he’s focusing specifically on innovative therapies in this example, I can see this argument being applied to biosimilars as well. It makes me wonder, had this harmonization been a priority ten years ago, would the U.S. biosimilar market be just as advanced as Europe? But it’s also important to consider the FDA’s stringency in terms of determining interchangeability and extrapolation. Though more regulatory unity could possibly speed the arrival of medicines to new countries, there are just as many ways this could also slow the uptake of biosimilars in less developed countries that desperately need cheaper health options.
EPIRUS Biopharmaceuticals created a splash in the industry when the company announced it would be terminating its Phase 3 development program for its infliximab biosimilar and refocusing on two biosimilars for rare disease drugs — Soliris and Actemra. The decision came because of the company’s diminishing funds and concerns over how developing such a widely used drug as infliximab would impact the company’s budget. A spokesperson for the company told The Boston Business Journal:
We can develop a biosimilar for rare diseases at a fraction of the cost of developing a biosimilar for the mass market. Moreover, the regulatory and development pathway is likely to be significantly less burdensome. And, perhaps most importantly, the demand and acceptance of biosimilars for rare diseases by patients, payers, and physicians is much, much stronger.
A number of industry experts have been discussing the impact this will have on competition, the growth of the biosimilar market, and on the (perhaps unsuccessful) future role of the pure-play business model. I don’t think this one example suggests the pure-play sector as a whole will be incapable of entering and succeeding in crowded markets. There are a number of other pure-play companies tackling development of the more in-demand biosimilars like adalimumab and infliximab. But EPIRUS’ move does establish an interesting and unique business model. The markets will be smaller and it will likely bring slower financial growth for the company (thus the reason this is a risky move for an already financially struggling company). But even Big Pharma has been drawn to the lucrative orphan drug market the past few years. The biosimilar versions of orphan drugs would likely be more lucrative than the first wave of biosimilars with a lot of competition on the market. This move will also benefit smaller, rare disease patient groups and will begin to bring more competition to the expensive orphan drug market, which has been a key part of the spike in drug prices. If biosimilars are being hailed as the answer to high healthcare costs, the orphan drug market should not be overlooked.
Medical Marketing & Media reports a number of drugmakers are expanding their efforts developing drugs for autoimmune disorders outside of the “windfall diseases” (i.e. rheumatoid arthritis and psoriasis). As knowledge about the structure and function of the immune system grows, more companies are setting sights on developing biologics for those with lupus, Celiac disease and 80-plus other autoimmune conditions. Payers are expected to play a significant role in how successful these drugs will be.
Payers will have a significant voice in what therapies providers select and patients use... Unless its price matches market growth potential, a drug touting ease of use is no longer sufficient to gain market attention.
The cheaper price of biosimilars is still expected to be alluring for payers, and as such, biosimilars could still come out on top of these more precision medicine versions of biologics. But biobetters are a topic of discussion at the upcoming World Biosimilars Congress in San Diego next Thursday and Friday, which I will be attending. If these meds continue to become more precise, it does pose the question if the less precise biosimilars will continue to be prioritized for even the "windfall" autoimmune diseases.
In a column in The Pharma Letter, Dr. Nick Meyers of Boyd Consultants discusses the impacts of the U.K. leaving the E.U. He emphasizes in particular the loss of biopharmaceutical R&D funding for the nation. Brexit could alter the relationship the country has with the European Medicines Agency, and it could add extra challenges for sponsors in conducting multi-center clinical trials in the U.K.
This piece is worth a read as we approach the June 23rd decision. From the grumblings I’ve heard from within the industry, and as Dr. Meyers touches on, Brexit would leave the U.K. hanging in terms of getting drugs approved. There are still ways the MHRA could be involved with the EMA in regards to drug approvals. However, there is also the possibility that the U.K. could end up constructing its own regulatory pathway. Should this be the route in the U.K., the biosimilar market could face slow growth in the years ahead — if the slow formation of the U.S.’s own regulatory pathway tells us anything. I plan on discussing the challenges Brexit poses for biosimilar makers more thoroughly in an article in the upcoming weeks — stay tuned!
The Pharma Letter reports the GPhA and the Biosimilars Council are at odds with the recent proposal from Centers for Medicare and Medicaid Services (CMS). According to The Pharma Letter:
The Medicare Program Part B Drug Payment Model proposed by CMS is a two-phase model that would test whether alternative drug payment designs will lead to a reduction in Medicare expenditures…Phase 1 would involve changing the 6 percent add-on to Average Sales Price (ASP) used to make drug payments under Part B to 2.5 percent plus a flat fee, in a budget neutral manner. The second phase would implement value-based purchasing tools similar to those employed by commercial health plans, pharmacy benefit managers, hospitals, and other entities that manage health benefits and drug utilization.
The GPhA is expressing concern over Phase 2 of this proposal in particular. Much like the CMS coding issues earlier this year, the GPhA doesn’t want to see biosimilar products compared to anything but their reference product. “Value-based” is certainly becoming a buzzword lately. I have my own concerns about how “value-based pricing,” for instance, could negatively impact biosimilars.
There have been a number of reforms in India, which could help the country develop high tech industries and lead to more R&D initiatives for private and public sectors. According to Swarajya, the government’s docket currently includes intellectual property reforms. There is also an ongoing campaign called “Make in India,” which, coupled with the government’s previous budget, has created R&D-boosting tax incentives. There are a number of reasons the country could bolster its innovative medicine development.
There is no reason why India cannot grow its own innovative bio-pharmaceutical sector. … The country’s relatively liberal regulatory regime makes it a promising location for stem cell research, cell engineering, and cell-based therapeutic R&D….Bangalore’s Biocon is close to releasing an insulin product that can be consumed orally. If successful, it could spell the end of the daily injections regime for around 387 million people with diabetes worldwide, including 67 million in India.
This was an interesting article that I urge you to read all the way through. Though there has been some growth in R&D spending in the country (it recently hit 6 percent), there is still a ways to go before it reaches the 20 percent typically spent by Western pharma companies. International partnerships are just one of the ways that could help increase the innovation in the country. These partnerships bring in new finances and skill sets that might not currently be available locally. I could see increasing emphasis on innovation being good for biosimilar development in India. The more novel biologics being created in-country, perhaps with the help of firms from more highly regulated countries, the more we could see increased quality and capacity in the country for biosimilar development.
According to MedPage Today, two U.K. trial centers have shown that Remicade biosimilar CT-P13 has demonstrated comparable efficacy and safety in patients that switched from the reference product. This switching was done voluntarily; patients were given the option of switching and agreed to it after discussions with their rheumatologists.
In one study from the University of Southampton, among 59 patients who switched from Remicade to the biosimilar Inflectra, 52 remained on the biosimilar 10.4 months later, reported Lucy Parker, MBBS, of University Hospital Southampton NHS Foundation Trust.
Positive results with switching also were seen in a second study presented in a poster session at the meeting by Ritu Malaiya, MBBS, of St. George's University Hospital in London. In her center, 30 patients switched to Remsima. Only one patient did switch back after reporting that she didn't feel she was improving, but her DAS28 had not changed.
Overall, there were very few cases discussed in this article in which patients had to switch back to the reference product because the biosimilar was ineffective or led to other issues. Similarly, as time went on and more data was amassed, there were no other reports of inefficacy. In fact, in the first trial, two of the patients that had to stop taking the biosimilar were suffering from issues that had arisen prior to the switch to the biosimilar. Though the biosimilar was not used to treat gastrointestinal issues in these trials, this data is still quite reassuring for those still concerned about interchangeability. A similar study held in pediatric patients demonstrated that switching between Remicade and biosimilar Remsima to treat inflammatory bowel disease confirmed the biosimilar's similarity to the biologic.
Ronald Piervincenzi of the U.S. Pharmacopeia (USP) and Thomas Menighan of the American Pharmacists Association (APhA), have written a column for Morning Consult discussing the negative impact the FDA and NIH Workforce Authorities Modernization Act could have on biosimilars. Primary concerns include the elimination of transparency and collaboration in the current regulatory landscape. For instance, should the USP public quality standards be eliminated, quality would be determined solely by the manufacturer and regulator — and these quality protections would not be made public. The authors write:
USP’s public quality standards support the development of new biosimilars because they provide manufacturers with a public quality benchmark in their product development. The public nature of USP’s standards makes it possible for quality to be tested by anyone at any point in the supply chain. In the absence of public standards, there only would be the private specification between a manufacturer and the FDA, and third parties such as global health purchasing organizations, law enforcement, distributors, and pharmacists would be deprived of an essential tool for identifying counterfeit and substandard drugs and ensuring the quality and safety of medicines.
I’ve heard very little about how this bill would impact biosimilars, in particular. I’ve heard the argument that speeding up the drug approval process could lead to safety issues. But I had not heard about the impact of the bill on the supply chain. Ultimately, when it comes to biosimilars, emphasis is being placed on just how much info should be made available to all parties outside of the FDA and manufacturer. Take for instance, the debate about including or not including comparability data in labels for doctors. On one hand, I can see how something like this empowers players in the supply chain to access information. Having access to public quality standards could also reassure them about biosimilar quality. This also suits the greater call for transparency within the industry. But on the other hand, I still gravitate towards the FDA’s Leah Christl’s reasoning behind not including comparability data in a biosimilar label. It could potentially confuse doctors or lead to misinterpretations of the data. Enabling a large number of parties to test and determine the quality of the product could lead to more concerns or factors that slow down biosimilar development and uptake.
There has been very little spoken about Shire’s intentions for Baxalta’s biosimilar portfolio following the announcement of Shire’s plan to acquire Baxalta. But there continue to be little clues that concern me about these candidates’ future. A recent BioPharma-Reporter article says:
Baxalta recently began shifting to an outsourcing model for at least its biosimilars business, offloading the Brooklyn Park, Minnesota facility it bought from Genmab in 2013 to Takeda in January, while Shire itself has invested heavily in-house. Only two weeks ago, the firm announced it intended to build a $400 million production plant in Ireland, complementing its internal manufacturing facilities in Massachusetts.
There is a chance that Shire’s increased capacity could be used to bring the biosimilar manufacturing in-house. But it’s also just as likely that since the business has already been shifted from Baxalta’s plate to CMOs, that Shire could easily decide it’s not in its capacity or best interest to continue holding onto them.
Boehringer Choosing Biosimilars Over Immunotherapy (4.29.16)
Boehringer Ingelheim confirmed with The Economic Times that instead of venturing into the highly competitive and lucrative immunotherapy race, the company will continue to focus its efforts on metabolic diseases and biosimilar drugs. This decision has come at a time when many big pharma companies have been trimming away the excess fat from their organizations to focus on key therapy areas.
Obviously Boehringer Ingelheim, with partner Eli Lilly, had success launching Basaglar, the first follow-on biologic to Sanofi’s Lantus. Just last November, the company announced its biosimilar candidate for Humira had completed Phase 3 enrollment, and its biosimilar candidate for Avastin (695502) is in Phase 3 as well. A rituximab biosimilar is currently undergoing Phase 2 trials (655066). The company is in the midst of interviewing for a new biosimilar executive to help guide its global biosimilar business, so I’m definitely expecting lots more to come from Boehringer in this biosimilar business.
As Big Molecule Watch Blog reports, the FDA has proposed modifying the application review process to be similar to that of the Prescription Drug User Fee Act (PDUFA) program. As the blog writes:
Highlights include a mid-cycle communication, a late-cycle meeting, and a review clock that begins on the 60-day filing date.
The mid-cycle communication could help with the transparency that biosimilar makers are demanding from the FDA. But I see the word “late-cycle meeting” and can’t help but think, does more personnel come with that plan? Because from what I’ve heard, there are already plenty of meetings on the books that already aren’t being kept.
In the meantime, on the small molecule generics side of things, Regulatory Affairs Professionals Society (RAPS) writes about the GPhA’s and contract manufacturers’ demands for the next version of the Generic Drug User Fee Act (GDUFA). Since 2012, there has been a backlog of roughly 6,000 Abbreviated New Drug Applications (ANDAs). The GPhA is calling for more transparency and predictability for the industry, and more access for patients. (Sound at all familiar to those on the biosimilar side of things?) These are all areas the GPhA feels have not been handled well by the FDA as of late.
It’s concerning that the generics industry is still struggling with some of the same issues the newly launched biosimilar market is — and the generics side has been around for decades. Those working on BsUFA negotiations are keeping this in mind. But it’s still unclear, given the FDA’s track record with generics, how exactly the biosimilar side of things will be able to negotiate itself away from these trends. Nor is it clear that biosimilar makers will be any better equipped to be able to hold the FDA completely accountable for not maintaining its timelines.
The approval of Inflectra in the U.S. for all indications, including the gastroenterology indications, was a win for biosimilar makers. This decision suggests that biosimilar makers will not have to spend the time and money determining how their candidates perform in trials for every indication. However, as BioPharma Dive discusses, despite the fact Zarxio was also approved for all indications, Inflectra faces some unique challenges because of this extrapolation decision. As Decision Resources Group’s (DRG’s) Kate Keeping discusses:
Gastroenterologists and rheumatologists are likely to be a lot more conservative about uptake than oncologists for several reasons. Oncologists can look to Europe, where biosimilar Neupogen has been used for almost a decade, compared with just a couple of years for biosimilar Remicade…Gastros have more concerns about indication extrapolation than rheumatologists, because Inflectra was not tested in gastro patients.
This shouldn’t be a surprise to anyone. If anything, it reinforces many of the concerns that were voiced during the FDA advisory committee review of Inflectra. The extrapolation to gastroenterology indications was a widely debated topic. However, the biosimilar is being used by gastro patients in Europe. It’s not as though the U.S. is the first country to make this decision, and there is data about the drug’s efficacy in Europe. Because of this, I’m not convinced that uptake will be as slow as expected.
Biocon had some good news and some bad news to announce this week. According to Biocon’s Kiran Mazumdar-Shaw, the company is looking to benefit greatly from Japan’s decision to market Biocon’s biosimilar insulin Glargine beginning in 2017. Shaw told Money Control:
This move will help foray into large emerging markets like South Africa, Brazil, Russia, and Turkey. She expects these markets to give Biocon sales upwards of $100 million from FY18.
The company is also at work on an oral insulin product, which it hopes to have before regulators for approval in the next two to three years.
However, on the cusp of this good news, the company also faces a setback for its trastuzumab biosimilar. As LiveMint reports:
Biocon can continue to sell and manufacture the drug, without calling their product ‘biosimilar’ and/ or ‘biosimilar to Herceptin, Herclon, and Biceltis’, or in any way ascribing any bio-similarity with that of the Roche products in any press releases, public announcements, promotional or in printed form, and from relying upon or referring the plaintiffs’ names.
The court was also critical about the role of Indian regulator Drug Controller General of India (DCGI) for approving Biocon’s version of Trastuzumab [in 2013] without applying the 2012 Guidelines on Similar Biologics and exempting the company from phase-1 and 2 clinical trials.
Biocon and partner Mylan have announced their intentions to challenge these orders, even though they will not affect the sale of the drug. This will impact the use of Roche’s data and the language within the label. This move is important from a quality standpoint, given India’s attempt to emphasize the quality of their medicines. Ensuring each drug candidate being approved — especially as a biosimilar — meets the clinical requirements is clearly important. Since Biocon has ambitions to enter other countries with its biosimilars, including the U.S. and E.U., providing the requested data could be important for other more stringent regulatory agencies.
According to Medical Xpress, half of Medicare patients taking a biologic for their moderate to severe plaque psoriasis stop within a year. This survey was carried out by the Perelman School of Medicine at the University of Pennsylvania.
The team looked at several factors that might have affected adherence and identified higher out-of-pocket costs as a strong possibility: Patients who were ineligible for subsidies under Medicare Part D (and thus responsible for high cost sharing) were more likely to be non-adherent and discontinue their biologic treatment. Female patients also were more likely to be non-adherent.
A recent Avalere study forecasted that biosimilar meds were going to be more expensive than reference biologics for Medicare Part D patients. There will likely be some legislative changes that will alter patient/Medicare/manufacturer cost sharing percentages in the future. But if Medicare patients don’t adhere to what are currently looking to be the “cheaper” reference products, biosimilars could be in for some adherence troubles of their own.
Brexit: Bad For Biosimilars? (4.22.16)
According to Tim de Gavre of the newly launched British Biosimilars Association (BBA), the U.K.’s withdrawal from the European Union (EU) would be harmful for the biosimilar market. According to BioPharma-Reporter, there are seven biosimilars in the EU, and none of them are produced within the country. Similarly, the production and use of biosimilars trail behind European countries like Norway and Denmark. As de Gavre tells BioPharma-Reporter:
[Brexit] would bring significant uncertainty both to approvals and launches of biosimilars. This uncertainty could delay market entry and potentially deny the NHS significant cost savings from these new products… It could also impact Britain as a clinical trial center and potentially also reduce companies’ willingness to conduct research in the U.K.
Considering the biosimilars available in the U.K. are all produced outside of the country, importing biosimilars from the EU could prove to be a nightmare logistically and financially. I hope to speak with a member of the BBA in the upcoming weeks more thoroughly about the impact Brexit could have for biosimilar manufacturers. But I’m also curious about the timing of the BBA’s launch during these discussions. Though encouraging the use of biosimilars is a key mission of the organization, I can only imagine the timing of this launch also had to do with protecting the biosimilar market amidst the Brexit discussions.
According to BioPharma Dive, the last six months have been good to Zarxio. A recent Decisions Research Group (DRG) survey showed Zarxio usage in the U.S. is on the rise. Upon approval, most doctors said they would hesitate to provide Zarxio within the first few months of its market launch. However, since them, every single doctor surveyed has prescribed the biosimilar to at least one patient in the six months post-launch. According to DRG specialist, Kate Keeping:
Oncologists in Europe have years of experience with Zarxio, and U.S. oncologists can reference this experience when making treatment decisions.
This shouldn’t come as a surprise. A few months ago, Sandoz was discussing how sales of Zarxio were a bit slow. But the drug’s successful performance in Europe has been credited many times for the quick FDA approval. It only makes sense that doctors would be encouraged by the drug’s performance abroad as well.
The FDA approved Celltrion’s Inflectra (infliximab) biosimilar in recent weeks. The biosimilar stands to prove a significant threat to Remicade’s market share, if the drop in European Remicade sales proves anything. (Sales dropped 8 percent last quarter alone.) However, like AbbVie, Janssen is putting on a brave face and remaining adamant that Remicade will hold its own in the U.S. because of its IP protection. Though Pfizer and Celltrion have an expected launch date of October 2 (or 180 days post-approval, thanks to Amgen v. Sandoz), Janssen is attempting to stall this launch. Remicade holds two unexpired patents, one of which dated to fall away in September 2018. The other is set for a 2027 expiration date.
Janssen has been pretty vocal over the past few months leading up to the FDA’s decision. The decision to extrapolate the drug for all of Remicade’s indications (minus pediatric Crohn’s) was particularly frustrating for Janssen. The company’s leadership might be cavalier right now, but it’s clear the company has concerns — especially about the extrapolation of these biosimilars. Since the drug is also available in the EU, there is plenty of data proving the drug’s efficacy in patients for all these indications. Prescribing doctors are only likely to be encouraged by its overseas performance upon its U.S. launch — whenever that might be.
A new article published in the scientific journal Regulatory Toxicology and Pharmacology highlights the findings of a doctor survey about biosimilar labeling. Similar to the U.S.’s recently released labeling guidance, EU biosimilar labels closely resemble the reference product label. However, of the 200 physicians surveyed in seven countries, more than 80 percent would prefer more data on a biosimilar label. As the EuropaBio press release states:
When comparing a standard label of an authorized biosimilar with a label containing additional relevant information (e.g. pharmacology, adverse events, dosage schedule and method of administration sections of the label), the vast majority of physicians (83 percent) preferred the one with additional information about what data had been generated with which product.
This data has the potential to prove reference makers’ arguments for different biosimilar labels. In fact, this data is discouraging to review when considering how the physicians in countries surveyed have had years of biosimilar experience. More than half — 59 percent — of these physicians had already prescribed a biosimilar. When the FDA reviews comments on its labeling guidance, one of the biggest suggestions will, no doubt, have to do with what data should appear within a biosimilar label. I’m sure some companies will likely include this data within their comments. After all, the survey’s sponsors — AbbVie, Amgen, Pfizer, Merck, Novo Nordisk, and Novartis — all have big interests in the reference-product side of things. But I’m still taking these results with a grain of salt. A recent European Crohn’s and Colitis Organization (ECCO) survey showed there had been an increase in the number of EU physicians that no longer believed biosimilars needed their own unique names. I would’ve expected that after 10 years doctors would be more comfortable with less data in biosimilar labels. But it makes sense that, since more complex biosimilars have yet to be rolled out abroad and in the U.S., more info will be desirable until there is enough evidence of more complex molecules’ efficacy and safety.
Congress is on the brink of finalizing a new bill that would allow generic drugmakers to update their safety labels as soon as new safety information comes to light. In the past, the originator drugs have been allowed to update their labels with new safety information. However, should a generic maker discover a new safety issue, they were unable to add these concerns to the drug’s label. As Regulatory Affairs Professionals Society (RAPS) writes:
If finalized, the rule as currently written would permit a sponsor of a generic drug to immediately issue a labeling change for any safety-related change (prior to FDA approving such a change), which begins a process intended to allow differences to exist between the generic drug, the brand-name reference product, and other approved generic drugs on a ‘temporary basis.’
This bill, which has been under discussion for over two years, has led to the ire of many in the generics industry, as the Hatch-Waxman act does not permit any generic drugs to have labels that differ from the originator. The GPhA has even threatened to sue the FDA for overstepping its “statutory authority.”
Now that biosimilars are on the U.S. market, I’m curious if and how these changes could impact biosimilar labeling. The recent FDA guidance on biosimilar labeling treats biosimilar labels much like generic labels. However, as Leah Christl of the FDA said in a blog, a biosimilar product is not required to have the same labeling as its reference product. For one, the biosimilar label will have a biosimilarity statement. It could also specify the biosimilar is not intended to cover every indication that the reference product does. At some point, there will also be a statement on the biosimilar’s interchangeability. Based on these facts alone, I get the sense that this proposed labeling rule will not apply directly to biosimilars.
India’s “Need For Speed” Draws Concerns (4.15.16)
The Economic Times reports that the newest version of the biosimilar guidance recently released in India aims to speed up the biosimilar review process. However, these efforts are being questioned by various companies and industry organizations. According to the Times, biosimilar approvals could be cut in half, dropping from 990 days to 424 days. As Reanjana Smetacek, the director of the Organization of Pharmaceutical Producers of India, says:
The 2012 Biosimilar guidelines were largely aligned with global requirements, whereas the proposed revised guidelines suggest dilution of some previous requirements and might potentially compromise patient safety.
A quicker approval process here — especially for something as new and tricky as biosimilars — is likely to raise a few eyebrows, especially given concerns about quality in the country. Ultimately however, it will come down to the data these companies are providing for review. The new guidance more clearly specifies the number of patients required to produce approval-worthy data and postmarketing data.
The FDA Voice discusses the growth of the Office of Generic Drugs (OGD) since the office’s expansion in 2015. The OGD released its first annual report, showing that the FDA approved more than 700 generics. As per its 2017 goals, the agency cleared 84 percent of its backlogged abbreviated New Drug Applications (aNDA). This, along with completing 88 percent of prior approval supplements (PASs), the agency is close to accomplishing 90 percent of the goals it set for 2017.
This is certainly good news to hear, especially as the biosimilar regulatory pathway becomes established. But this track record is already a concern. If the generics industry has been established for more than 20 years and this kind of backlog exists, that doesn’t bode well for the biosimilar industry. Already the agency, by its own admittance, underestimated the resources it would need to meet the emerging biosimilar regulatory demand. We can celebrate the OGD’s progress, but it can also serve as inspiration to ensure your company’s input gets heard during the ongoing BsUFA negotiations.
According to The Weinberg Group, the Biosimilar User Fee Act (BsUFA) negotiations have been making progress since December 2015 when the first meeting was held. Members from BIO, PhRMA, The GPhA, The Biosimilars Council, and The Biosimilars Forum recently met with the FDA to discuss negotiation ground rules and timelines and to learn more about FDA BsUFA “enhancements.” The FDA’s goals for BsUFA include:
- A negotiation process that supports timely reauthorization;
- Enhancements to capacity and coordination of review for biosimilars;
- Enhancements to biosimilar review process communication, consistency and efficiency; and
- Financial stability for the biosimilar review process with predictability for the FDA and fee-payers.
I’m glad to see communication and predictability on here. Arguably, these are the biggest complaints from industry members about the biosimilar review and approval process. But what will also be important, which several of these organizations have called for, is more transparency into how the biosimilar review process is being financed, and how the FDA plans to go about enhancing their meetings management, review timeless, and meeting performance. My recent interview with Bert Liang, CEO of Pfenex and the chair of the Biosimilars Council also emphasized the importance of the FDA's performance in meetings.
BioPharma Dive held its first “State of Drug Development Survey,” which charted the responses of 850 biopharma and life sciences researchers. According to the results of this survey, biosimilars are considered the most promising therapeutic class. Roughly 25 percent of respondents believe biosimilars to be the most promising treatments emerging, followed by PD-1/PD-L1 (21.1 percent), T-cell receptors (20.3 percent), CRISPR-Cas9 (13.8 percent), CAR-T (8.7 percent), and PCSK9 (7.5 percent).
I don’t find this particularly surprising, though it was interesting to see this come in above immunotherapy treatments. If this survey had been taken last year, I think the immunotherapy and PCSK9 would’ve been high up on everyone’s “most promising” lists. I’d bet Humira’s upcoming patent expiration mixed with the U.S.’s second biosimilar approval has definitely drawn more eyes toward biosimilars.
Last week, I questioned what would happen to the Shire-Baxalta merger in the face of new government tax inversion rules. I stumbled upon my answer to that question this week — only a week later than the Daily Mail got to it:
Irish drug company Shire has insisted its £23billion takeover of Baxalta is still going ahead following the collapse of the biggest deal in pharmaceutical history earlier this week.
I haven’t heard much other than this. There’s also still no word about what this takeover will mean for Baxalta’s biosimilar pipeline.
The Korea Herald reports that the Denmark drug procurement agency Amgros selected Samsung’s etanercept biosimilar for rheumatoid arthritis. This is good news for the company, as:
Benepali, Samsung’s biosimilar version of Amgen’s top-selling Enbrel, is expected to take away at least 50 percent of the original drug’s market share in Denmark, as local hospitals and doctors favor prescribing drugs selected by the procurement agency, [an industry source] said.
I wrote about Denmark’s procedure for determining drug tenders in a recent article. I’d imagine the reason the procurement agency holds as much clout with doctors is because physicians play a huge role in the tender-awarding process for prescriptions. Considering doctors have a lot of concerns over biosimilar clinical data, the country’s strategies for enabling doctors to interact with that data and question it can only help promote biosimilars to other physicians.
Also, given the biosimilar uptake in Norway and Denmark, this is, obviously very good news for Samsung. Seems as though it’s hard to make it through a work week without hearing about some new triumph from Samsung.
A new report from Avalere Health has found that Medicare Part D patients are likely going to have to spend more on their biosimilar drugs than the reference biologic. According to the report, Medicare Part D patients taking biosimilars will likely have to pay upwards of $1,500 more per-year than those taking the reference biologic. Avalere has come up with two possible legislative changes that could help cut down on patient costs. These include:
Requiring manufacturer discounts to close the coverage gap for biosimilars, consistent with current law for branded drugs; and creating a biosimilar tier that would reduce beneficiary costs for the biosimilar to the same level as the reference product.
I plan to feature a longer piece fledging out the details from this report next week, as well as my thoughts on the solutions offered. Stay tuned!
Seeking Alpha highlighted AbbVie’s up-and-coming pipeline, and it looks like the company is doing its best to replace Humira with another “Humira.” The company’s pipeline currently consists of four candidates that all are targeting the same conditions for which Humira is approved. These candidates are: ABT-122 (psoriatic and rheumatoid arthritis), ABBV-257 (rheumatoid arthritis), ABT-494 (for those that don’t respond to TNF inhibitors), and ALX-0061 (rheumatoid arthritis and lupus).
ABT-494 is the farthest along, and is currently being studied in several Phase 3 trials. I give props to AbbVie for trying to stick to what it knows best. This is certainly a stretch, but should one of these prove to be as much a miracle as Humira, the company could easily squash biosimilar competition. In fact, this brings up a question I’ve had for a while now: could biosimilars still be preferred in the face of a better, next-gen “Humira”?
An article in BioWorld reveals that none of the top 20 drugs sold in China are innovative biologics. While the country has approved 96 biologics, one expert says that 99 percent of these are “copies, not even biosimilars.” This shouldn’t necessarily alienate biopharma from China, however. As Michael Yu, founder and CEO of Innovent Biologics, describes:
Monoclonal antibodies (mAbs) are the fastest growing segment in China. The MAb market grew by 40 percent between 2010 and 2013, according to Equity Research data, capping off at $670 million in 2013. Yet with only 6 percent market penetration in China, mAbs are a great growth opportunity, Yu said.
I recently wrote an article focusing on biosimilar pure-play, amp biosimilars, which carries out a lot of its development work in China. I’ve had my eye on this territory as a potential hotbed for biosimilar uptake. It seems Yu is of the opinion that China holds great potential for biologics and is “just waiting to be supplied.”
Pharmacy Practice News features an article about the latest FDA approval of its first infliximab biosimilar. One of the biggest questions still remaining after this approval, however, is about what the FDA will require to determine interchangeability. In its approval of Celltrion’s biosimilar, the FDA specified that it had not been deemed an interchangeable medicine. According to Bernstein analyst Ronny Gal (who, as this week’s news will prove is an oft-quoted figure in this space!), there are ways drugmakers can determine interchangeability.
A classic way to test interchangeability, [Gal] said, would be a four-arm trial: one arm using the innovator product, one receiving the biosimilar, and two arms switching back and forth on opposite schedules.
This is a decent strategy to be sure. From a recruitment standpoint, I could see this format being a curse. I did read in a Law360 article recently that switching studies are becoming more commonplace — at least according to Sandoz. In the article, Sandoz battles an assertion AbbVie made that very few switching studies have actually been carried out. According to Sandoz, there have been 58 switching studies for five biosimilars treating a grand total of 12,000 patients. Those are impressive numbers — though I do not have the source where Sandoz received its information.
The government’s new initiative aims to educate and boost physicians’ confidence in biosimilar medicines. The project has a budget of $20 million, and it will be carried out over the next three years. The country has taken some steps to ensure uptake, including adding nine biosimilars to the Prescription Benefits Scheme (PBS). Though these biosimilars are not considered interchangeable, a recent State Government Health Department tender has recommended that infliximab biosimilars be doled out to treatment naïve patients. According to Bird & Bird, the National Health Act specifies that, when it comes to biosimilar naming:
Active ingredients of biosimilar medicines will use the Australian biological name (without a specific biosimilar identifier suffix).
Well done, Australia. I’ve been keeping this country on my periphery since Australia moved to permit substitution at the pharmacy level last June. You can find my write up about this decision here.
The mega-merger between Allergan and Pfizer was called off because of new government efforts to curb corporate tax inversions. According to USA Today, it’s still uncertain how these new rules will impact other companies that have completed similar deals. As USA Today reports:
Shares of Ireland-based pharmaceutical firm Shire fell 2.3 percent to $173.47 and Baxalta shares closed down 7.4 percent at $38.50 as the new restrictions also cast doubt on Shire's pending bid for the U.S. company.
There were a lot of questions about how Baxalta’s biosimilar candidates would fare up against Shire’s desire to become the rare disease goliath. In looking at their combined pipelines, the number of biosimilars seemed measly in comparison to what the rare disease portfolio would be following the merger. This has led to a speculation about whether Shire would choose to eliminate the biosimilar unit. If these new rules make inversion much less appealing, we might not need to worry about the fate of Baxalta’s biosimilars after all.
Celltrion revealed that 2016 will bring trials for Avastin and Humira biosimilars. The company is labeling these two assets the “second wave” for the company. The company’s “first wave” comprised infliximab, trastuzumab, and rituximab biosimilars. As Business Korea writes, Celltrion is fairly late in the game for Humira biosimilars. However, as an official at Celltrion writes:
Some analysts say that the patent expiration on Humira is imminent, but we judged that quite a few patents including formulation patents still have a considerable period remaining until expiration.
I know I’m not the only one to question this move to focus on Humira. Undoubtedly, Humira is a treasure trove. But even if there are years to go before the maze of patent protection disappears, there will likely be a large lineup of approved candidates just waiting to hit the market. At this point in the game, being one of the first few players on the market holds an advantage. We can’t know for certain, but with the number of candidates already in late stage clinical trials or up for approval already, this doesn’t seem like the smartest move for Celltrion.
A few weeks ago, Samsung was the focus of an article in FiercePharmaAsia. The company has been praised for its ability to rise in the biotechnology ranks and grab the first approval of a biosimilar for Enbrel in the EU. The company’s VP of the process team, Brian Hosung Min, shared some of the reasons for the company’s success:
A key strategic move in the process end of development, Min said, was the decision to scour the globe for a large supply of originator product well before development started that yielded 127 different lots of Enbrel from sources in Europe, the U.S. and the rest of the world (RoW). This allowed the company to run 57 chemical assays and 27 biofunctional analysis in parallel, greatly speeding up the ability to set a comparator benchmark into what would become Benepali.
Really interesting process — one that cuts straight to the heart of biosimilar development. If it’s all about the comparative data, may as well home in on that from the get-go.
According to FiercePharmaMarketing, the FDA’s recent biosimilar labeling guidance might be disappointing for both reference product and biosimilar makers from a marketing perspective. While comparative clinical data was not deemed necessary for a biosimilar label, according to Bernstein analyst Ronny Gal:
For larger companies with strong marketing muscle that hoped to use their more robust clinical program as a commercial differentiator … this would be more challenging with this data not on the label.
If companies are capable of attaining approval with “less robust” clinical programs, this seems to fit well into the argument for fewer biosimilar clinical requirements. If it cannot even be used to help biosimilar makers compete against each other for market share, it would make sense we’d see more companies hoping to save money by avoiding more complicated clinical efforts. As many have said, the FDA’s guidance certainly separates biosimilars from marketing their drugs along the same lines as biologics. But Gal hits the nail on the head when he says: The "most likely trajectory" is "early development along branded lines with later transition to generic-like market structure."
As FiercePharma writes, branded drug makers have developed a solution for fending off generic competition for some of their big moneymakers. According to Fierce:
Instead of offering up discounts to retailers and wholesalers, [Teva] went straight to payers with the price break — in exchange for brand exclusivity versus Copaxone's first generic competitor, Sandoz's Glatopa. The result? ‘When Sandoz showed up with a traditional discount to the channel, it found out those buyers could not shift volume to its products as the determination of preferred product was made by the payers,’ Bernstein analyst Ronny Gal said.
These are not biologics, but the strategy could very well be representative of a struggle biosimilar makers will have getting onto the market. There are some dangers to this process though. As Gal highlights, if there’s no room for generic competition, price wars are likely to ensue. That said however, given the attention to high-priced biologics and the differences between biosimilars and small molecule generics, the pricing drops aren’t likely to be as high. (The price cuts Gal suggests would be 70 to 80 percent.) But if that’s the case, this suggests competition among biosimilars would be severely limited.
For those of you looking for a recent tally of pending state substitution applications, the National Law Review writes:
According to a recent tally by the National Conference of State Legislatures, at least 10 bills related to biosimilars (either newly filed or carried over from 2015) are pending this spring, many of which are very similar to laws already in effect in other states.
Kentucky was the most recent state to approve biosimilar substitution. Rather than simply permitting the pharmacist to substitute a biosimilar for the reference product, Kentucky actually requires the substitution unless otherwise specified by the physician. New Jersey and Puerto Rico were the other most recent and were passed late last year.
Samsung Bioepis, along with parter Biogen, has launched its first suit in Britain against AbbVie to bring its Humira biosimilar to market more quickly. The company tells Reuters:
We believe that AbbVie has been attempting to obstruct market entry of competing products by applying for a large number of overlapping patents around Humira, which could affect patient access to affordable medication. We believe competition should take place in the market, and not through such misuse of the patent system.
We hear so much about evergreening within the insulin market. Even though there have been a number of challengers against AbbVie’s fortress of Humira patents, I don’t know that I’ve ever heard this referred to as a “misuse” of the patent system. As much as I’d like to see biosimilar competition, the inability of others to tackle Humira’s patents in recent months leaves me a bit skeptical about Samsung’s chances. At this point, these “misuses” of the patent system are starting to seem like a very well-crafted business approach.
The European Commission’s CHMP reviewed the biosimilar, named Flixabi (infliximab), for approval in the EU and adopted a positive opinion. The drug will now be available on the market to treat rheumatoid arthritis, adult & pediatric Crohn’s disease and ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.
The Korea Herald also reported this week that Samsung Bioepis is poised to launch its second biosimilar, Renflexis (infliximab) in Korea. The drug will be priced at $315 a box (a 5 percent discount from Remicade), and will hit the market in June.
The FDA has finally taken a stance on biosimilar labeling. The FDA has taken stock of both biologics and biosimilar makers’ demands for what a label should or should not contain in the new guidance, and biosimlar makers should be breathing a sigh of relief. There is some emphasis on expressing the difference between a biosimilar and biologic in the label. The FDA’s Leah Christl writes:
One of the first items health care professionals may notice in the Highlights section is the addition of a “Biosimilarity Statement” describing the biosimilar product’s relationship to its reference product.
However, the FDA's decisions on what clinical data is needed (or rather, not needed) on a biosimilar label is quite telling. For instance, the FDA argues that:
Data from clinical studies designed to support a demonstration of biosimilarity are not likely to be relevant to a health care practitioner’s considerations regarding safe and effective use of the biosimilar product and potentially may cause confusion, resulting in an inaccurate understanding of the risk-benefit profile of the product. For example, the endpoints used in a clinical study intended to support a demonstration of no clinically meaningful differences may not be the same endpoints studied to support approval of the reference product and may not inform prescribing decisions regarding safety and efficacy.
Overall, the FDA expects a biosimilar label to address the differences between the biosimilar and its reference product, while also avoiding bogging down the label with excess clinical data that could cause slow uptake. The fact that the only clinical data needed on the label is that of the reference product is a huge win for biosimilar makers. I'm actually somewhat surprised by the FDA's decision here, given the agency's decision to favor the biologics' makers arguments about the need for different names. But while this is a win for biosimilar makers, I do have some concerns about the fact that physicians currently are craving more clinical info. While I’m not in support of including comparative data on the label, it seems to me that the lack of inclusion could cause physician concerns (or suspicions) and stall uptake.
According to Law360, Sandoz has sent a letter to the FDA over AbbVie’s recent argument that interchangeability of biosimilars can only be determined following clinical research in every indication. Law360 writes:
The BPCIA authorizes an interchangeability designation only if a biosimilar ‘can be expected to produce the same clinical result ... in any given patient.’ ‘The most logical, harmonized reading [of those sections] is that a biosimilarity license permits a demonstration in only one [indication], while an interchangeability determination requires that every [indication] be addressed,’ AbbVie's petition said. However, [Sandoz] focused on the ‘can be expected to’ language. According to Sandoz, instead of directly studying every indication, a biosimilar maker simply needs to produce data that would make one expect the same clinical result.
Two words for you: Abbreviated pathway. The biosimilar pathway will not be abbreviated (or feasible) if companies are expected to produce all the information AbbVie expects.
Biocon announced approval of its biosimilar insulin glargine in Japan, making the company the first non-multinational corporation to have a biosimilar approved in the country. There are currently three companies that offer this biosimilar insulin. In an interview with CNBC’s Money Control, Kiran Mazumdar Shaw, chairperson and managing director of Biocon, states that this approval lines the company up very nicely for an approval elsewhere, including the U.S. She says:
Of course what this news also means is that our filings that we are going to submit in the very near future both for U.S. and European regulatory approval will no longer be a question mark. This means that we will enter those markets sooner than later because this endorses the quality of the product and the quality of the dossier and because of the Japanese approval we believe we can enter almost any ROW market.
The U.S. is in dire need of some cheaper diabetes treatments, but I’m not entirely sure that an approval in Japan will guarantee the product’s approval in the U.S. — at least not anytime soon. Look at the caution the FDA had in the face of approving its first biosimilar, and in that situation, it had 10 years of EU data backing up filgrastim’s efficacy.
Regulatory Professionals Affairs Society (RAPS) announces that India’s Central Drugs Standard Control Organization has released a new draft of its biosimilars guidance which was previously issued in 2012. The revision included several major changes, two of which center around postmarket updates and fermentation process development. As RAPS writes:
CDSCO is calling for specific postmarketing safety data ‘through a pre-defined single arm study of generally, more than 200 evaluable patients and compared to historical data of the Reference product. The study should be completed preferably within 2 years of the marketing permission/manufacturing license unless otherwise justified.’ The primary aim of the Phase IV study is safety, CDSCO says, noting that the primary endpoint should be safety while the secondary endpoint should be efficacy and immunogenicity.
For manufacturing, the guidance has now termed “fermentation process development” as “Upstream process development,” keeping all requirements under this name the same.
As FiercePharma reports, the survey of European Crohn’s and Colitis Organization (ECCO) members survey shows that doctors have grown much more comfortable with biosimilar interchangeability.
It found that 44.4 percent of physicians taking the survey considered the Remicade biosimilar, a mAb, interchangeable with the original product. That compares to only 6 percent who that felt that way in 2013. Only 19.5 percent of respondents had little or no confidence in the use of biosimilar monoclonal antibodies, down from 61 percent who gave that response in 2013.
These stats should give hope to those pursuing biosimilar development, especially those looking to launch biosimilars in the U.S. The growth in comfort over interchangeability in as short a time frame as 3 years is, frankly, stunning. In the ECCO abstract, there are a number of trends to note, including the fact that only 35 percent of physicians now believe that biosimilars should carry unique International Nonproprietary Names (INNS) compared to a whopping 66 percent in 2013. These data show that so many of the hoops the U.S. is jumping through currently, such as designating complicated naming and labeling policies, very likely will go against doctors’ inclinations and needs in the upcoming years. Data like these also illuminate the absurdity of the update the WHO has made to its biosimilar naming policy. These policies are clearly not guided by or for those who will be responsible for actually getting these drugs into patients’ hands.
Decision Resources Group (DRG) presented some of the key points from the 8th Biosimilars Congregation held in London in early March. The DRG article focused on Remsima/Inflectra Uptake, the need for Phase 3 clinical trial data, and developing physician and payer trust in biosimilars. But what caught my eye was what DRG writes about the latter topic:
During the conference it was highlighted that physicians and payers are largely unaware of the batch-to-batch variability of biologics.…
This has struck me time and time again in the debate about biosimilars. Each batch of biologics that is manufactured has differences from the previous batch. It’s as if each new batch of a reference product is a biosimilar of the previous batch. This is obviously something that is being emphasized when it comes to biosimilars, and indeed is one of the reasons that could keep doctors from prescribing them. But yet, there’s no concern about patients receiving a biologic that has been manufactured in a different batch. If we’re educating doctors about the differences between the reference product and the biosimilar, then there should probably be education about the minor differences that exist between each batch of the reference drug as well.
Celltrion Now Dubbed Big Business In Korea By FTC (3.21.16)
According to The Korea Herald, Celltrion is due to become Korea’s first “homegrown” biopharmaceutical company that has been classified as a big business. The company’s asset value reached $4.3 billion last year, meaning the company has reached the threshold of what the Federal Trade Commission (FTC) considers to be a “large corporation.” Celltrion’s status is set to change by April 1st. The company had previously pinned its profit growth to increasing use of its Remsima biosimilar.
This is interesting timing given the recent challenge raised against the company’s financials by Ghost Raven Research. Fortune recently picked up this story, which I discussed in a blog post last week. There have been very few other publications that have discussed Ghost Raven’s claims, and as the group holds a short position in Celltrion’s stocks, this is likely just a money scheme. But it struck me as fishy these accusations should occur right as the company is poised to become a big business.
FirstWordPharma reported this week that Eli Lilly’s CEO, John Lechleiter, met with Samsung Bioepis and Samsung BioLogics to discuss “coordination efforts” for biosimilars. This meeting led to speculation about a new biosimilar partnership taking shape. However, according to various reports today, this speculation has been chalked up to rumors. As BioPharma-Reporter writes, Samsung stated:
We would like to clarify that this was a courtesy meeting that did not involve any discussions about potential cooperations or partnerships.
This all strikes me as fishy. From some of the chatter I’ve heard about this deal, the fact that both companies have a Lantus biosimilar would make a partnership an issue in terms of anti-trust laws. But for a company like Lilly, which has been slow so far to build up its biosimilar business (Basaglar being its first and only to date), tackling its portfolio with the help of Samsung — a rising star — would be a smart way to go.
According to Regulatory Affairs Professionals Society (RAPS), Eastern Research Group (ERG) released a report revealing the FDA’s biosimilar workload from 2013 to September of 2015. This workload includes biosimilar product development (BPD) meetings, policy efforts, 351 (k) reviews, and education efforts, among other tasks. There are roughly 60 products in development and in discussion with the FDA to date. The FDA has spent $81.7 million and 295 full-time equivalents (FTEs) on these efforts, of which biosimilar development program activities required the greatest workload.
One of the biggest issues FDA has identified was not having a large enough workforce to tackle the increasingly popular biosimilar division. However, it seems as though the Senate health committee is attempting to fix this issue through the FDA and NIH Workforce Authorities Modernization Act. Chairman Lamar Alexander states:
This bipartisan bill takes a significant step to improve FDA and NIH’s ability to deliver on the promise of this exciting time in science, by helping them hire and retain top performers and cutting red tape that actually obstructs their ability to keep up with the newest scientific advancements.
“Newest scientific advancements” meaning biosimilars? Here’s hoping.
According to three Hogan Lovells experts in a Lexology column, the FDA has outlined how it plans to transition protein products that were approved using a New Drug Application (NDA) or abbreviated New Drug Application (aNDA) to section 351 of the Public Health Service Act. These products include insulin and somatropin, among other products. Biologics such as these that have been approved via NDA will be replaced with Biologics License Applications, and they will be considered . It’s important to note, however:
FDA does not take a position in the draft guidance on how it will determine whether an approved NDA will be deemed to be a 351(a) biologic or a 351(k) biosimilar, which has significant implications for protein products approved under 505(b)(2) NDAs. Similarly, it might be presumed that ANDA products would be deemed to be 351(k) biosimilars, but the draft guidance is silent on that issue as well.
The deadline for this is March 2020, so there is still time for companies to receive final approval for any biologics under review using the NDA or aNDA for approval. For instance, Eli Lilly’s and Boehringer Ingelheim’s Insulin Glargine follow-on biologic was approved using an NDA. Had it still been in consideration for approval by the deadline, it would’ve been “deemed to be a license” and would’ve lost any market exclusivity (should it have been labeled a biologic, rather than a biosimilar).
In a new blog post, FirstWord Pharma’s Duncan Emerton discusses the insights he gleaned from chairing Virtue Insights 8th Biosimilars Congress. As is to be expected, there were a number of uncertainties discussed by experts on panels at the event. But there were two interesting tidbits of information that caught my eye. For one, Emerton discusses how “regulatory evolution” is occurring outside of the U.S.
In countries like Egypt, regulatory standards are being aligned with the EMA biosimilar guideline. Elsewhere the focus is likely to remain on supporting local industry. Providing better access and developing ‘local drugs for local people’ remains a critical need.
I was really struck by the notion of biosimilars being “local drugs for local people.” They become both a cheaper alternative and a form of national identity. This is why the Trans-Pacific Partnership agreement and India’s supposed promise to avoid compulsory licensing deals are harmful to the biosimilar market.
Emerton also discussed the clinical trial side of things. There were numerous discussions about whether a future in which biosimilar makers do not need to provide clinical data to regulators would ever be a possibility. Emerton writes:
For simple products, including insulin and filgrastim, many presenters, experts, and delegates generally agreed that this would be possible. Where MOAs are well understood, there are limited issues with immunogenicity and the pharmacodynamic endpoints are well established, clinical studies would not be needed. Where products are immunogenic and work via a number of MOAs, clinical studies would be needed. A key issue for complex products is that immunogenicity can’t be tested in vitro, so studies for mAbs and other proteins that illicit an immune response will continue to be needed.
This is not going to be an easy battle for biosimilar makers to fight — at least not any time soon. There is data to back up certain biosimilars’ successes in Europe over the past few years. But I can imagine with the lack of knowledge among patients and physicians, as well as the warnings about differences between reference product and biosimilar, getting rid of clinical trials altogether will not be likely for many years. However, we should still be heartened by the FDA advisory committee’s recent thumbs up to extrapolation for Celltrion’s infliximab biosimilar. The first step to no clinical data is surely getting a biosimilar approved for all conditions without clinical data for every indication.
Pharma is no stranger to the efforts of Kyle Bass, the hedge fund manager who has made a strategy of challenging patents via the Inter Partes Review (IPR) process and shorting company stocks. However, it seems there’s been a new challenge launched against a specific biosimilar maker in an attempt to make a few bucks as well. According to a research group that I plan to keep anonymous for now, a company known for its biosimilars has been lying about the strength of its financials. This group writes that the company financials are ~90 percent lower and that operating costs are 50 percent higher than what the company has originally claimed.
However, also written clearly in the group’s disclaimer is that it holds a “short position in all stocks and bonds…and therefore stands to realize significant gains in the event that the price of either declines.”
The company has since responded, claiming that the accusing group likely lost significantly in the face of the company’s successes, and, therefore, is attempting to reap the benefits of casting doubt on the company’s performance.
There’s been little to nothing written about this accusation since these rumors were launched, which is partially why I wish to keep the parties anonymous/the stories unlinked. I don’t wish to draw excess attention to these likely faulty claims, or the groups involved in them. However, this got me thinking about the rising number of challenges being used to weaken companies by targeting their stock price. This reminded me strongly of Kyle Bass’ attempts, and I’m curious to see if this becomes another method of attempting to stall biosimilar makers’ progress to market. In looking through the group’s documents cache however, it is only focused on this single biosimilar maker (unlike Bass who has targeted a number of different companies). This makes the whole situation seem as though it could’ve been launched by an angry ex-employee.
FiercePharma writes that Centers for Medicare and Medicaid Services (CMS) has announced a new Medicare reimbursement scheme. CMS plans to launch pay-for-performance and indication-specific reimbursements for cancer drugs in order to prioritize “clinically superior” meds. As FiercePharma writes:
Normally, doctors get reimbursed the average sale price of a drug plus a 6 percent premium, which some say encourages them to choose expensive therapies. The new plan would lower the premium to 2.5 percent and add a $16.80 fee. The proposal is now in a 60-day comment period. SunTrust analyst Yatin Suneja said in a note to clients. The CMS' move ‘could reduce incentives for physicians to prescribe expensive medications such as oncology drugs and biologic therapeutics,’ Suneja said, especially when similar, cheaper meds are available.
CMS might have ruffled some feathers over the biosimilars naming policy. But if the procedures eliminate incentives for prescribing brand name drugs, this could help push biosimilars more quickly into patients’ hands. However, there are also some elements to this that could be problematic for drugmakers seeking to extrapolate a biosimilar to cover a reference product’s label. As CMS described:
A cancer therapy ‘might be used to treat one condition with high levels of success but an unrelated condition with less effectiveness, or for a longer duration of time. The goal is to pay for what works for patients.’
For biosimilars that are extrapolated for multiple indications, this could add more performance pressure, or in the end lead doctors to favor new drugs that are proving highly beneficial in certain therapeutic areas — take for instance IL-17A or JAK inhibitors that are started to make their way onto the market.
STAT writes that Austin, TX has seen nearly 200 life science companies launched within the city over the past few years. Though a large number of the companies starting out in Austin are small, the growth of the industry begs the question: Could Austin be the next big biotech hub? Among other tax and climate benefits, the region is also soon going to be home to the Dell Medical School.
The influx of new clinicians, Austin Technology Incubator’s Cindy WalkerPeach argued, will give local startups a resource to help make their products relevant to health care. ‘I think what’s been missing is that unique insight into what patients need and what clinicians need,’ she said.
I see a lot of promise here for biosimilar makers. Since physician education is such a concern for the industry right now, being part of a biotech community that is soon to have a large number of up-and-coming physicians within reach could bode well for makers.
According to The Korea Herald, Amgen Canada has dropped its patent infringement suit against Samsung Bioepis in Canada. The suit was targeting Brenzys, a biosimilar of Enbrel, which had been submitted for approval to Canadian regulators. The Herald writes:
With Amgen stepping back, Canada’s medicines agency is set to resume reviewing Brenzys as planned. If approved, the Korean drug maker is expected to debut the new drug in the North American country.
This would be the drugmaker’s first entrance into the North American market. The biosimilar in question was recently approved and launched under the name Benepali in Europe.
In a recent submission from the U.S.-India Business Council to the U.S. Trade Representative (USTR), India “privately reassured” it would not allow local generic firms to override patents and manufacture generics of branded drugs, Reuters reports. These compulsory licenses are often granted in the face of public health emergencies. The release of this news has led to disapproval by Medecins Sans Frontieres and other non-profits/patient organizations that are concerned this assurance will harm needy patient populations.
The country made the USTR’s watchlist for two years, as the USTR believed India was dismissive of patent laws in favor of bolstering local generics makers. I’d be curious to know what led to these private promises — and if the promise will be kept. I’m also wondering if this decision could quell the number of Indian players entering the biosimilars game.
China continues to prioritize improvements to the country’s pharmaceutical quality by announcing new regulations for generic drugmakers. According to YIBADA, generic drugs that are currently approved and on the market must be assessed by drugmakers to determine that they are the same quality as their brand medications. Once similarity is proven, the drugs will be added to the government’s insurance program and prioritized.
Similarly, drugs that treat diseases like HIV, cancers, and rare drugs will be prioritized for CFDA review following receipt of an NDA.
Under the regulations, drugs that already have ongoing registration application in the U.S. and EU will be given the same status, provided that their production facilities have already passed on-site inspection by the two regions’ drug monitoring bodies. Priority will also be given to drugs that are to be used in the treatment of particular diseases…as well as those that have current urgent demand.
Like biosimilars, perhaps? Not only does this requirement bode well for companies looking to forge partnerships in China, but if there’s an increasing push for generics in the country, a rule like this can help regulators and doctors prioritize biosimilars. Granted, the one big downside to this is that it will be costly and time-consuming for the manufacturers.
An article in FiercePharma highlights how brand makers have used Risk Evaluation and Mitigation Strategies (REMS) to halt generic competition. However this could have a great impact on biosimilars as well. According to a recent study carried out by the Generic Pharmaceutical Association (GPhA):
In 2014 drugmakers used REMS to protect brand drugs from 40 small molecule drugs [worth 5.4 billion]. About 40 percent of FDA-approved drugs are now subject to REMS, and, the impact on biosimilar development could be enormous. ‘It undermines the whole generic drug approval process,’ Steve Giuli, an executive with generics firm Apotex told the Associated Press.
First the TPP with data exclusivity, and now this.
This month, Kentucky joined the increasing list of states to pass a bill allowing pharmacists to swap an interchangeable biosimilar for a branded biologic. However, the bill also contained a rule that could prove problematic for biosimilar uptake. The Kentucky Center for Investigative Reporting writes:
The bill retains a provision requiring pharmacists to notify prescribing doctors of any switches to interchangeables within five days. The Kentucky Pharmacists Association opposed the provision, saying that the notification requirement would be burdensome enough to discourage substitutions. ‘Prescriber notification requirements have shown to increase costs for the healthcare system overall because they result in more brand dispensing,’ said Bob McFalls, executive director of the KPhA.
To my knowledge, this isn’t the only state with this provision written into this bill. However, I stand with the pharmacists on this one. The more work that has to be done to swap a biologic with a biosimilar, the more likely a pharmacist will stick with routine biologic prescribing habits. This is where payers could play a helpful role. (Of course this is all a moot point until the FDA figures out what interchangeability means and approves a biosimilar as interchangeable.)
Nearly 50% Of Physicians To Prescribe Biosimilars In Next 3 Years (3.4.16)
A new survey released from InCrowd highlights physicians’ expected biosimilar prescribing habits. In a breakdown of the results, BioPharma-Reporter reveals that pricing will be a key factor in getting doctors to prescribe a biosimilar. According to the survey’s results:
A majority (83 percent) of the 150 doctors who took part in the survey by market research firm InCrowd said they would prescribe a biosimilar if it were 25 percent cheaper than the reference product, while only 33 percent said they would take such action if the drug in question was five percent cheaper.
However, we are also to expect that doctors will show some brand loyalty, as well.
Nearly half of respondents expect to prescribe biosimilars to a greater proportion of their treatment-naïve patients than to patients currently or previously treated with the originator bioloigcs, 30 percent and 38 percent, respectively.
This is encouraging data, given past surveys that have demonstrated the lack of knowledge doctors currently have on biosimilars. In the U.S. today, Zarxio only stands at 15 percent, which is still 10 percent away from the target 25 percent. This is a good sign that, even though 25 to 30 percent discounts on biosimilars are still low when compared to small molecule generic discounts, this will be good enough for prescribing physicians to turn to biosimilars.
According to an opinion piece published in The New York Times last month, it’s high time we should see generic competition for insulin, as well as a more transparent process for pharmacy benefit manager (PBM) drug pricing. As Kasia Lipska, an endocrinologist at Yale School of Medicine, writes:
In the United States, just three pharmaceutical giants hold patents that allow them to manufacture insulin: Eli Lilly, Sanofi and Novo Nordisk. Put together, the ‘big three’ made more than $12 billion in profits in 2014, with insulin accounting for a large portion. What makes this so worrisome is that the big three have simultaneously hiked their prices.
Lipska does overlook the fact that the U.S. has approved its first follow-on biologic, Basaglar (insulin glargine). But she hits on the key need for cheaper competition in the insulin market. Similarly, her discussion on the questionable motives of PBMs and the need for increasing attention (or enforcement actions from the Federal Trade Commission) is worth a read.
The Pew Charitable Trusts has published a Q&A. Though most of the Q&A is just covering the basics about biosimilars, it did also address the implications of states choosing not to allow biosimilar substitution at the pharmacy.
Research indicates that limiting the substitution of conventional generics decreases uptake and increases drug prices. One study found that requiring patient consent reduces rates of generic substitution by 25 percent. The same study concluded that state Medicaid programs could save over $100 million if patient consent requirements were eliminated for three top-selling drugs. Another study found that the submission of “dispense as written” requests (which require a pharmacy to dispense a specific brand among two or more interchangeable products) is associated with unfilled prescription rates and higher costs.
Though these findings are not unexpected, it’s still good to see them spelled out like this. (You can find the original data in this article catalogued in the NIH Library of Medicine.) It seems as though, at the end of the day, both biosimilars and biologics lose if patients don’t select generics and physicians’ dispense as written requests aren’t always filled.
Amgen has filed a suit against Sandoz’s biosimilar of Enbrel in the District Court for the District of New Jersey. The company has claimed that the biosimiar is infringing on some of its Enbrel patents, and as such, should not be able to be sold if/when it is approved. According to FiercePharma:
The way Amgen sees it, Sandoz is ‘piggybacking on the fruits’ of its ‘trailblazing efforts’ in developing Enbrel, the company said in the suit. Amgen, for two decades, has been working on the drug, which treats a range of autoimmune diseases including psoriasis and ankylosing spondylitis. But Sandoz has only conducted clinical trials of its biosimilar for psoriasis patients, despite the fact that it wants it approved for a host of indications, Amgen alleged in its suit.
The 501k pathway was formed to be an accelerated approval pathway for these cheaper alternatives. Sandoz needs to “piggy-back off the fruits” of Amgen’s innovation, considering the end goal for a biosimilar is to demonstrate “fingerprint-like similarity” to the reference product. Amgen’s concern is probably the worst argument I’ve read so far — especially from a company that is creating its own biosimilars.
FierceBiotech reports that Merck has launched a Phase 3 trial for its MSB11022 in chronic plaque psoriasis. The study will recruit roughly 400 patients in Europe, Asia, and North/Central America. It’s still hard to determine what the competitive landscape will look like in terms of biosimilars on the market, however this move raised a few eyebrows. As FierceBiotech writes:
Merck's candidate, known as MSB11022, is not looking to replicate all of the drug's licenses, but is currently focused on just treating chronic plaque psoriasis…. It's behind most of the big players in terms of development. And the fact that it's starting small with just one license means sales will likely to be modest — but this is a steady start to a relatively new unit which the firm will hope can shore up revenue in the future.
This move was met with general confusion, given the number of players currently attempting to get Humira biosimilars to market. Surely, at some point, there are going to be too many players on the market to hope for a profit — and Merck is not anywhere near the front of that line. (I’ve heard anywhere from seven to 12 more advanced candidates in development for Humira.) Similarly, the strategic decision to just seek an approval for psoriasis seriously limits the drug, given it’s 8 other indications. Though other companies might not be targeting every indication for their own biosimilar, the FDA’s recent extrapolation decision for Celltrion’s infliximab could open the door to more players opening up their candidate’s labels using less clinical data. I will say however, the way this info is presented here makes it sound as though this biosimilar is simply a test-run for an independent Merck after its high-profile biosimilar partnership with Samsung.
According to The Pharma Letter’s India correspondent, India’s biosimilar market has seen more than $900 million in sales, making it a promising market for biosimilar makers. The correspondent also highlighted that:
Around 10 pharma players are intensely competing in this area with around 15 epoetin, eight G-CSF, and four insulin biosimilars.
These sales have risen considerably since 2008, when biosimilars raked in roughly $338 million. But in another article published last week in The Business Standard, one consultant argues that India will not see as great a success as the country did with its global generics business. In fact, Utkarsh Palnitkar expects that innovator companies that jump into biosimilars will see better success. He references the cost and number of biosimilar clinical trials in particular. He states:
Let us assume, even if it is a smaller, limited set of trials if you have to do in Europe or the US, that will negate the entire cost advantage that Indian companies have. Then a pot of gold at the end of the day seem like a few coins. The biggest cost of drug development is clinical trials. Purely in my opinion the innovator companies when they come up with their own [biosimilars], will probably stand at an advantage.
According to Pharmabiz, the Central Drugs Standard Control Organization (CDSCO) plans to release guidelines on biosimilars within the next couple of months. These guidelines will provide the quality, preclinical studies and clinical trial requirements of “similar biologics” in India.
I’ll admit I’m a little surprised to hear that India has yet to launch any guidelines for biosimilars, especially given the amount of work being done with biosimilars within the country. As one expert on Twitter also called attention to in this story, the choice to call biosimilars “similar biologics” is intriguing. The article bounces between biosimilars and similar biologics. I’m personally hoping that they just stick to biosimilars. The last thing the bio space needs are more names for biologic drugs (bio-betters, follow-on biologics, biotech generics, bio-identicals, similar biologics… etc. etc. I'm hoping it doesn't get any longer.)
STAT features an interview with CVS Health’s CMO and EVP Troy Brennan about the company’s efforts to cut client costs over the past year. In the interview, Brennan highlights some of the medicines that saw the greatest uptake and largest price increases.
A couple really caught our attention — dermatological and diabetes. There are a lot of brand-name medicines in both categories with a lot of background inflation and especially increasing utilization. In diabetes, we see a lot of patients started on more expensive branded medicines, instead of metformin, which is an older, expensive treatment. So what we can do is put new prior authorization programs in place that are more sophisticated than the ones we had before in order to reduce utilization.
If there was some process in place to eliminate the evergreening that is pervasive in the IP for diabetes meds, this inflation problem could be solved by insulin biosimilars. But even more concerning here, however, is that doctors are turning to newer meds rather than the cheaper options. Despite the fact there is only one biosimilar (or rather, follow-on biologic) insulin on the market right now, if CVS is altering its authorization programs to emphasize price over brand, we could see some hope for biosimilar uptake in this therapeutic area… whenever the biosimilar insulin space is more populated.
In order to gain greater market share, many biosimilar companies have been launching switching studies. These studies aim to prove that patients taking the reference biologic can be just as sufficiently treated by the biosimilar. According to STAT:
Sanford Bernstein analyst Ronny Gal said some brand-name drug makers may fight back by threatening to withhold valuable rebates on their other products from insurers that choose to cover a rival biosimilar medicine. But by pointing to switching studies, biosimilar manufacturers can argue that insurers would lose money if they don’t cover the lower-priced alternatives for both existing and new patients. ‘From a commercial perspective, you can’t really succeed in the marketplace without switching existing patients,’ Gal said. ‘The battleground will be the patients.’
There wasn’t a great deal of new information about the concept of switching studies in this article, but it’s good to read publically that more companies are pursuing switching studies. Up to this point, Norway was getting all the attention in terms of launching switching studies. Now we’ve heard Celltrion is pursuing its own, which is good to note seeing as it’s likely going to be one of the forefront players in the U.S. market to start off.
Medscape published an interview with Seth Ginsberg, the president and co-founder of Global Healthy Living Foundation and its arthritis division, CreakyJoints. In the interview, Ginsberg gives his thoughts on the recent FDA Arthritis Advisory Committee’s recommendation to approve Celltrion’s infliximab biosimilar for all indications on Remicade’s label. Ginsberg tells Medscape:
We spoke in favor of this recommendation, but we would have preferred that the committee followed Canada's lead and not recommended approval of it for Crohn’s disease.
I wish Medscape had pushed for more here. Safety is likely the main concern, but considering the fact it has demonstrating its efficacy in all indications in the EU for many years prior to the FDA, I’m not sure what the hang up is here. I think if there were a follow-up article from a patient representative for those with Crohn’s disease (CD) or ulcerative colitis (UC), I think we’d be reading a very different argument. I did, however, appreciate Ginsberg’s discussion of how the science behind a biosimilar might not be enough for the patient. He states:
Scientists are evaluating the similarity using data and statistics. There may be a minimal or inconsequential difference between a reference biologic and its biosimilar. However, to a patient who has tried and failed to respond to multiple biologics and has finally identified one that works properly, even the most minuscule difference between that medicine and its biosimilar could cause the biosimilar to fail. We also need to respect the fact that the patient has most likely spent years finding a biologic that works and so will be hesitant to try something new when the current biologic is working.
This is a valuable point to remember, especially in the age of patient centricity. From the patient’s point of view, the experience is going to come before the science—even if that science is bullet proof. But in this particular case, when we already have evidence of its efficacy, I still don’t feel that this is a good enough argument to keep cheaper biosimilars off the table for patients who are seeking treatment for CD or UC.
According to The Pharma Letter, New Zealand’s Pharmaceutical Management Agency, or PHARMAC, is seeking proposals from suppliers of insulin glargine — including biosimilar insulin glargine. Before August 2015 when delisting restrictions/subsidy reduction expired for Sanofi’s Lantus, PHARMAC had an agreement with Sanofi-Aventis. However:
Restrictions on delisting and subsidy reduction for Lantus and Lantus SoloStar ended on August 1, 2015. PHARMAC says it is aware of biosimilar presentations of insulin glargine which are currently seeking regulatory approval or being launched in other countries meaning that competition in this market is now imminent.
Since Basaglar is the only biosimilar insulin out there right now, this would be a good opportunity for Lilly and Boehringer.
Modern Healthcare discusses the rising interest in value-based pricing. As drug prices reach alarming heights, more drugmakers, like Novartis, are exploring linking a drug’s price to its performance. However, this is proving to be a challenging system to establish. As the article describes:
But building value-based payment structures has been far from easy and likely won't become any easier for pharmaceuticals. For instance, the Entresto deal will involve changing the prescribing behaviors of cardiologists, who are accustomed to using cheap, effective generic drugs and may be less inclined to switch to the more expensive Entresto.
I’m all for this country trying out some new pricing models. But it strikes me that this could be problematic for biosimilars, especially if it comes down to swaying doctors away from prescribing cheaper drugs.
FDA Launches Biosimilar Education Course (2.19.16)
According to the FDA Voice, the FDA has initiated a new Continuing Education Course for health care professionals entitled “FDA Overview of Biosimilar Products.” Those taking the course will learn about interchangeability and the differences between biosimilars and generics. Leah Christl, associate director for therapeutic biologics in CDER’s Office of New Drugs, writes:
This course also will help health care professionals understand how a biosimilar can be prescribed and dispensed, and how and when an interchangeable product can be substituted for another biological product. The program will inform healthcare professionals about the development process and approval pathway for biosimilars and interchangeable products. It also includes information about FDA’s general review process for these products.
Glad to finally catch word of some educational efforts underway at the FDA. This joins the efforts of the Biosimilar Forum, which recently announced it has launched a new education initiative called “Partnership for Biosimilars Education and Access.”
According to Pulse News, Celltrion has experienced upwards of a 60 percent jump in net profits for 2015 over 2014, an increase that was fueled by increasing shipments of Remsima. The company saw $164.8 million in net profits. Sales have also increased since exporting 464.4 billion won worth of Remsima to Europe last year.
This should serve as encouragement for Sandoz, which announced less exciting sales figures a few weeks ago. (Keep in mind, as well, that Zarxio was only released in September.) The exciting part of Celltrion’s news is that Remsima has only been on the market in the EU for a year. To see such a huge jump in profits after a single year on the market gives hope for those that have braved being the first players on the market, despite regulatory and market uncertainty. In the U.K. after a single year, the infliximab biosimilar has a 16 percent market share, Biosimilarz blog editor Duncan Emerton recently shared on Twitter.
Following the Amgen v. Sandoz ruling last summer, Sandoz has petitioned the Supreme Court to review the legitimacy of a ruling that biosimilar makers must wait an additional six months after the drug’s approval to bring their biosimilar to market. The argument between biosimilar makers and innovators is if the company needs to wait until the drug is actually approved by the FDA to give its mandatory 180-day notice of commercialization. However, the FDA Law Blog poses some concerns about what could happen should the marketing provision be upheld:
Reference product sponsors may find (and argue for) new ways to apply it, perhaps in the context of supplemental applications submitted to FDA seeking changes to a licensed Section 351(k) biosimilar product. Such supplemental applications may seek changes to the manufacturing process of a biosimilar product, or to add into labeling an indication previously omitted because of unexpired patent or non-patent exclusivity (e.g., orphan drug exclusivity) protections on the reference product. Why not argue for a 180-day notice in those situations as well?
This gives me a headache just thinking about it. It sounds like a lot of extra hoops to jump through, but it’s not far from reality when thinking about what innovators have been doing so far to stall biosimilars from hitting the market.
For those of you keeping up on the continuing patent-dance legislation, Apotex has responded to Amgen’s response to its opening brief opened before the Federal Circuit in December. Goodwin-Proctor’s Big Molecule Watch blog reported in December that the District Court granted Amgen’s motion requiring Apotex to wait 180 days to market its biosimilar — but only once it has received FDA approval. (The drug is still awaiting an official review date with the FDA.) Apotex has been arguing that it should not have not comply with this 180-day commercial marketing provision because it engaged in the patent dance with Amgen.
As is to be expected, Apotex has appealed this decision with the Federal Court, and just filed its reply brief to Amgen’s statement released earlier this month. Both briefs are linked to in the latest Big Molecule Blog post.
The work to develop oral biologics has been underway for decades, PMLive reports. However, researchers have still not managed to find a feasible way to ensure the drug makes it through the destructive stomach and intestines to reach the appropriate therapeutic targets. There have been a few success stories, including Ironwood Pharma’s peptide drug Linzess/Constella (linaclotide); Chiasma’s Octreolin, and Tarsa Therapeutics’ Ostora. There are a few more ongoing efforts we can keep our eyes on though, including:
Novo Nordisk and Merrion are working on an oral formulation of insulin based on the latter's GIPET technology, an absorption enhancer designed to help large molecules cross from the GI tract into the blood, and recently entered their candidate into phase IIa trials. Novo Nordisk is also working with Emisphere Technologies on oral delivery for an oral version of semaglutide, a GLP-1 agonist that recently completed a phase II study. Other companies developing oral insulins include Diabetology Ltd which has taken a product called Capsulin based on Proxima Concepts' Axcess aromatic alcohol-based absorption enhancer technology in trials, as well as Israeli company Oramed whose ORMD-0801 candidate is in phase II.
I’ve heard a lot of talk in the past about the concept of a “needle pill.” MIT and Massachusetts General Hospital have been working on this capsule containing tiny stainless steel needles embedded in an acrylic shell. There are efforts to use nanoparticles, and Rani Therapeutics and Novartis are at work on a “robotic pill.” (This actually sounds a lot like MIT’s work because it also contains tiny needles.) In fact, Novartis is working on applying “robot pill” technology to its own biologics. Could be cool to one day see this technology, if successful, move over to Sandoz, too. The introduction of oral biologics/biosimilars — especially for more complex antibodies — would be revolutionary and a great competitive tactic for the companies launching them.
I stumbled across three different reports that would likely be of interest to some of you. I’ve linked to them here for your reference.
Several months after Pfizer cut its infliximab biosimilar development program in order to acquire Hospira, Sandoz has decided to bolster its own biosimilar program. PF-06438179 is currently in Phase 3 development. FierceBiotech writes:
Novartis' move marks another threat to Merck, which markets the Johnson & Johnson-invented Remicade in Europe. Merck's Remicade revenue dropped 24 percent to $1.8 billion last year as it contended with the early days of biosimilar competition, and the U.S. drugmaker has been slashing prices around Europe to defend its position.
The key here is that Sandoz bought rights for the drug in Europe. After its recent update on financials and the slow uptake of Zarxio in the U.S., this should serve as a nice financial boost for Sandoz — especially, considering the threat infliximab has posed against Merck thus far in Europe. Also, this acquisition rounds out Sandoz’s pipeline quite well, giving the company all of the anti-TNF treatments.
Sandoz has filed its fifth biosimilar application to European regulatory authorities. The EMA announced its acceptance of the application and has begun to review the data for the pegfilgrastim biosimilar. According to the company, this filing marks the halfway point towards the goal of filing 10 biosimilars from its late-stage pipeline. Amgen is on the defense, however. As PMLive writes:
Amgen has been trying to defend Neulasta from competition with the launch of the Neulasta Onpro kit, which includes a single dose of the drug and a disposable injector system worn like a patch on the arm. It avoids the need for a return visit to the doctor the day after chemotherapy is administered... Launched last year, the new formulation accounted for almost a quarter of all Neulasta prescriptions in the U.S. in the fourth quarter.
Sandoz already has filed for approval in the U.S., where the patent for Neulasta expired in 2015. It makes more sense why it chose to file for the unpredictable U.S. market first, rather than the E.U. where the patent is in place until 2017. Granted, the U.S. market is also a bigger market for Neulasta sales than Europe. This new method of administration seems to have become favored among doctors if it already accounts for a quarter of sales (though I’m sure there was an increase in the drug’s price, as well). Until interchangeability gets figured out, a biosimilar version in the U.S. is likely to face competition — at least for current patients — from this upgraded version.
According to Mike Palmedo of Infojustice.org, Obama’s 2017 budget proposes that biologics exclusivity be lowered to seven years, rather than 12. The budget also pushes to eliminate the process of evergreening, which grants extra exclusivity to biologics due to slight changes in formulation. However, as Palmedo states:
Although past budgets have proposed shortening the term of exclusivity for biologics, the Administration has not really pushed to actually change the law here. This illustrates the problem with the use of trade agreements to bind the country to norms on intellectual property that exceed those negotiated in TRIPS. If trade officials succeed in committing countries to an eight or twelve year period of data exclusivity, then other government officials lose the option to really reduce the period back to seven years.
The official budget can be found here, with the reference to reducing biologics exclusivity mentioned on page 36. Judging from the fact this has appeared in past budgets without any change suggests it won’t be happening this year, either — especially since the TPP text has been finalized. It’s a nice dream at least. We kind of shot ourselves in the foot there by not remaining firm on seven years in the first place.
Despite all the concerns about whether Celltrion’s biosimilar infliximab would gain the gastroenterology indications, the FDA’s Arthritis Advisory Committee gave the biosimilar a nod for all indications on the label. (The pediatric ulcerative colitis indication is Remicade’s last, lingering patent. This indication will be clear in the U.S. in 2018.) An article in BioWorld shared some highlights from the hearing. For instance:
Panelist Jogarao Gobburu, a professor at the University of Maryland School of Pharmacy, suggested the FDA use a word other than extrapolation. ‘Extrapolation implies no data. That is not the case,’ he said. ‘We have data.’ Once a follow-on establishes that it is highly similar to the reference product, it shouldn't have to prove safety and efficacy over and over again for all the indications, he added.
I liked Gobburu’s discussion here, and I’ve never heard anyone suggest changing the term extrapolation to something else. But the concerns about extrapolation extend far beyond the word — though I loved the use of the word “Extrapolated” in a Bloomberg article this week titled “J&J Gets Extrapolated.” Sounds like something out of a Terminator movie. Overall however, this decision is great news for the biosimilar market in the U.S. There were concerns we would follow in the footsteps of Canadian health regulators who decided not to approve the drug for all indications because of a few slight differences. While extrapolation will still be decided on a case by case basis, this suggests that biosimilar makers won’t have to put their candidates through numerous trials to get full label approval.
According to The Indian Express, Biocon is nearing the end of Phase 3 studies for four of its nine biosimilar candidates (being developed in partnership with Mylan.) According to the chairperson of Biocon, the company expects to file for FDA and EMA approval by the end of 2016. The Indian Express writes:
Biocon will be filing for regulatory approvals in these markets in a phased manner during 2016 for four biosimilars — Trastuzumab (to treat breast cancer), Pegfilgrastim (for chemo-induced Neutropenia), Adalimumab (for chronic plaque psoriasis), and Insulin Glargine.
The U.S. has already seen Basaglar approved as a follow-biologic of insulin glargine. But given the state of the generic insulin market (as in there really isn’t one), this would be an interesting development for the U.S. Plus, it could hold the title of the first “biosimilar” insulin, rather than follow-on biologic. Similarly, the U.S. has yet to see any applications for Trastuzumab. In fact, you don’t even hear much about biosimilar development programs for Herceptin, though Biocon's would be up against Samsung’s trastuzumab biosimilar, which is slated to finish Phase 3 clinical trials in May of this year. Biocon could make a name for itself in the biosimilar space in the U.S. if it gets these candidates accepted for review by the FDA as early as it plans.
In briefing documents released prior to Celltrion’s infliximab biosimilar hearing, the FDA claimed the product was “highly similar.” In particular, Regulatory Affairs Professionals Society (RAPS) reports:
The Agency noted that Celltrion has provided an ‘extensive data package to address the scientific considerations for extrapolation of data to support biosimilarity to other conditions of use suggesting that CT-P13 should receive licensure for each of the seven indications for which US-licensed Remicade is currently licensed and for which CT-P13 is eligible for licensure.’
Approval seems imminent, and frankly, extrapolation seems logical. Given the biosimilar’s uptake and use as a successful treatment for all indications overseas, the U.S. should take the chance.
In a committee hearing, Janet Woodcock, director of the FDA’s CDER, revealed that the FDA did not receive any additional funding to begin building the biosimilar review program following the approval of the BPCIA. As more players enter the ring, the FDA has received an increasing amount of funding through user fees, however Woodcock still has concerns about the FDA’s financial readiness as the market continues growing. Regulatory Affairs Professionals Society (RAPS) reports:
‘I’m concerned this program is going to explode,’ Woodock said, referring to the fact that FDA doesn’t have the staff to keep up and is always playing catch-up with companies submitting biosimilar applications, though more funding will come in as the market becomes more robust in the U.S.
Woodcock refused to directly answer Rep. Pallone of NJ’s final question of if the FDA needs appropriations from Congress to successfully carry out its work on biosimilars. But I’d say her tone was sign enough. (You can view the full hearing here.) The establishment of the BPCIA was a huge step for the United States in terms of addressing rising healthcare costs. The fact that Congress didn’t provide funding to establish a biosimilar review program from the start, however, says a great deal about this country’s priorities when it comes to cheaper healthcare and biosimilars. The FDA has been receiving flak for not accomplishing all it needs to in order to firmly establish the BPCIA. Clearly some of this blame has been misplaced.
According to Sheng Li and Irena Royzman of Patterson, Belknap, Webb, & Tyler, the WHO has released a new naming policy that resembles the FDA recommendation — though there are a few key differences. The article highlights:
The WHO proposes to add a “biologic qualifier” (BQ) suffix, which consists of four random consonants and an optional two-digit checksum, to the nonproprietary name of each biologic and biosimilar product. The checksum is calculated based on an algorithm that takes into account each of the four randomly assigned consonants and their positions in the suffix. For instance, if a biosimilar was assigned the suffix “bxsh” and that suffix is associated with a checksum value of 08, the national regulatory authority would have the option of using “bxsh,” “bxsh08,” or “bx08sh” as a BQ identifier.
I dare say I’m not the only one puzzled by, or, rather, dumbfounded by this new proposal. The goal for adding a suffix to a biosimilar was to make it less complicated to identify and track biosimilars. Parties in the U.S. are already rallying against non-meaningful suffixes because they could cause confusion and lead to transcription errors. But the WHO for whatever reason feels that including a checksum, which can be put in the middle or at the end of a non-meaningful suffix, would be less difficult to transcribe than the abbreviation of a manufacturer’s name. Unpack that logic for me.
According to BioPharma-Reporter, AbbVie expects that if Celltrion’s infliximab biosimilar is approved in the U.S. for all indications as Remicade, extrapolation in all major markets will follow. In fact, Dr. Steinar Madsen, medical director at the Norwegian Medicine’s Agency, tells the publication:
Extrapolation is an essential element for biosimilars. When developing a biosimilar, you essentially can save money and time by doing fewer clinical studies, as compared to the originator. Usually, this [data extrapolation] is not very controversial, considering that the mechanism of action is usually well known. There is in most cases no reason to believe that the originator and biosimilar will behave differently. However, extrapolation must be justified on relevant scientific evidence in all cases.
Steiner puts one thing into very clear perspective: extrapolation would make biosimilar development more affordable and, therefore, more appealing for companies to continue entering the market. However, on the other side of this, if extrapolation becomes more common place, too much competition could be more harmful than good to the market. Approving more biosimilars will likely introduce more pricing competition, leading to greater discounts and healthcare savings. But it’s still uncertain whether the biosimilar industry, with its higher development costs, will be sustainable with as much competition as the small molecule generics company.
Goodwin Procter’s Big Molecule Watch Blog reports that Japan’s Ministry of Health, Labor, and Welfare aims to lower generic and biosimilar pricing.
Under the proposed plan, generic drugs will be priced at 40 percent of brand-name drug prices, while ‘[b]iotechnology-based generics, such as genetically modified drugs, will be initially priced at 70 percent.’
Japan’s 30 percent reduction is in line with what we’re seeing so far in Europe, where pricing tends to fall between 15 and 30 percent. While it’s certainly not even close to Norway’s pricing, this is still coming in higher than the U.S. where Zarxio is available at a 15 percent. Granted, discounts will likely go up a bit more as more competition enters the U.S. market.
Sandoz has been in the spotlight since it released its first biosimilar in the U.S.—a move that many companies were likely skittish to do, because of the lack of clarity surrounding biosimilar uptake in the U.S. However, the company experienced flat net sales in the fourth quarter. FiercePharma cites Bernstein Analyst, Ronny Gal, stating:
The fact that the unit has been leading the biosimilars charge could be part of the issue. Biosimilars are ‘coming in a bit slow’ overall, Gal wrote. So despite having the first and only such product on the market — Zarxio, a copy of Amgen's Neupogen — de-emphasizing ‘simple generics’ in favor of biosimilars has made for a gap in launches.
Flat sales are a better than falling sales. But considering they’re “leading the biosimilar charge” right now, praise is due to Sandoz for taking one for the team.
AbbVie recently announced that Humira saw a boost in the U.S. before its fourth quarter financials. However, internationally, where there is competition from infliximab biosimilars, Humira saw a 13 percent drop. In response to this slight drop, CEO Richard Gonzalez argued that IP protection would prevail in keeping sales secure. BioPharma-Reporter cites Gonzalez stating:
Across all of the litigation aspects of Humira, I think it’s important to recognize that we have now entered a new phase of our biosimilar strategy. The most important thing here is that we prevail…Our responsibility is to make sure that we put the best position forward and that we don’t tip off our opponents in this process as to what our strategy is.
It makes sense to remain mysterious about the specific details of the biosimilar strategy for competitive reasons. But I find Gonzalez’s statement that AbbVie is trying to keep its strategy under wraps amusing, considering there isn’t any clear indication of what their strategy even is at this point. All we really know at this point is that they’re releasing more innovative novel drugs, rather than a biosimilars of their own. But what was their first phase, let alone their second?
Four months after Zarxio hit the market, Amgen reports that it still holds 76 percent of the filgrastim market share. However, this is after several declines in both worldwide sales (4 percent) and U.S. sales (11 percent). Amgen remains optimistic, while also acknowledging it expects some losses. Anthony Hooper, EVP of commercial operations told investors:
We’ve had competition on the market for over a year now plus a biosimilar competitor for close to six months. And we still hold 76 percent of the market share. We will compete account by account using our many years of experience competing against biosimilars in Europe and branded competitors globally, but do expect some share loss.
This loss will surely be gradual at best. For instance, last week, a Sandoz spokesperson said Zarxio is performing in the market as expected, and that because it’s a physician-driven market, “We fully expected more gradual uptake.” Translation: sales are off to a slow and probably not a great start. As it was with the small molecule generics market however, we’re in it for the long haul. Biosimilars certainly weren’t going to be an overnight success.
FirstWord Pharma reports that Samsung Bioepis and partner Biogen have agreed to offer their biosimilar of Enbrel, Benepali, at a 47 percent discount in Norway. The country made waves last year at this time when Orion Pharma agreed to sell its infliximab biosimilar at a whopping 72 percent discount. As the publication says: “Pfizer’s decision to discount aggressively in response, however, is most telling.”
I’m excited to hear more about Pfizer’s discount as the news becomes available. Norway dances to its own drummer, so it’s hard to expect what has happened there will carry over to other countries. But to see a reference drug maker lower prices on their biologic shows the biosimilar industry is serving its purpose of lowering the price of healthcare.
Kevin Noonan, a partner at McDonnell Boehnen Hulbert & Berghoff told BioPharma-Reporter to expect the FDA to be cautious about extrapolation moving forward. While Zarxio won approval for all indications, he states:
[The FDA] may be thinking that the European experience with this first class of drugs is something of a safety net for testing whether there may be sufficient danger or uncertainty that clinical trials for all indications are necessary, desirable, or prudent. The lessons learned from the current crop of biosimilars may not be so directly applicable to new biologic drugs, and the severity of any problems that arise will influence — if not determine — whether this practice will continue.
Noonan addresses a pretty big question many are asking: Is Zarxio’s approval indicative of how biosimilars will be approved moving forward? He's also spot on here. Given the FDA’s caution over naming and its emphasis on the science being “bulletproof,” the agency is likely to limit extrapolation on biosimilars that haven’t previously been released in the EU.
Last week, a press release announced that a new university would be launched in China in order to train Chinese sterile injectable drug manufacturers to comply with new regulatory requirements. This week, BioPharma-Reporter launched a follow-up to this announcement. According to an analyst cited in the article, the country will see more facilities closing due to an inability to meet Western quality standards. However, larger players and CMOs are likely to benefit the most from this training university, putting China on the map for injectables. COO of PaizaBio, David Deere, says:
Today, [China] is the largest supplier of API [to the West], while India is the largest supplier of finished pharmaceutical product. China wants to ‘leap frog’ the Indians and focus on biologics and large molecules which are the hardest to make and the most valuable.
China could become a hot-spot for biosimilar development, especially considering the number of pure play and small biotech players working on biosimilars that will need the assistance of CMOs. I’ve been hearing from some experts that China holds a lot of promise in terms of biosimilar development. I’ll be discussing this in an upcoming From the Editor article, so stay tuned!
The National Institute for Health Care Excellence (NICE) is recommending the NHS cover seven biologics for the treatment of severe rheumatoid arthritis, including AbbVie’s Humira, Merck’s Remicade, Pfizer’s Enbrel, and two infliximab biosimilars. However, NICE has specified these drugs should only be prescribed for patients with severe RA, not moderate cases, and that patients should be started on the least expensive option. (*cough* biosimilars *cough*)
Obviously this is exciting news for those targeting the U.K. with their anti-TNF biosimilars. Many in the industry are hailing this as key step for the promotion of biosimilars. How could it not be, considering NICE chose not to include moderate cases of RA in their recommendations for these treatments — a move that disgruntled the reference drug sponsors. After the FDA’s “middle-ground" — but mostly innovator-favoring — stance on biosimilar naming, it’s refreshing to see a regulatory body putting biosimilars first.
The Korea Herald reports that biosimilar maker Samsung Bioepis is considering delaying its public listing on the Nasdaq. The company originally planned for the listing to occur within the first six months of 2016. The Korea Herald writes:
According to news reports and sources, the company is unlikely to pursue its debut on the world’s second-largest stock exchange this year, possibly due to the volatile U.S. biotechnology market and its own patent disputes… Analysts say a pending legal dispute with U.S.-based pharmaceutical giant Amgen in Canada could be one of the factors affecting Bioepis’ IPO plan...
The company’s IPO was supposed to help fund more R&D for the company. So I find this news discouraging — especially since Samsung is poised to be a great player in the biosimilar space. We’ve been hearing about the possibility that litigation could slow the biosimilar market, and we could be seeing the effects right here.
In The Biosimilarz Blog, FirstWord Pharma’s Duncan Emerton discusses some of the biggest questions circulating through the industry as Celltrion’s infliximab biosimilar nears its FDA review. These questions include whether Zarxio’s approval is the appropriate benchmark for approval, and if CT-P13’s controversial history will influence FDA thinking. In particular, Emerton writes:
Controversially, Health Canada did not award all indications to CT-P13 when approved in January 2014 due to a ‘small difference in the amount of afucosylated mAb.’ [While this difference was not considered clinically meaningful,] CT-P13 was only approved in Canada for rheumatology and dermatology indications, with gastroenterology indications being excluded from the final label. When it comes to what influenced Health Canada’s decision, one has to mention a J&J sponsored article which essentially argues that data from rheumatology indications cannot be extrapolated to gastroenterology indications. Will these arguments influence FDA thinking? Time will tell.
Emerton presents a thorough breakdown on CT-P13’s regulatory history, so I encourage you to read the whole blog posting. In a recent interview posted on First Word Pharma, he discusses NICE’s recent guidance, which essentially prioritized two infliximab biosimilars for the treatment of rheumatoid arthritis. However, Emerton expects this will not have a massive impact on biosimilars in the U.K. because rheumatoid arthritis only accounts for 20 percent of infliximab usage. The vast majority of patients on infliximab are being treated for gastroenterology conditions (ulcerative colitis or Crohn’s). J&J’s argument that rheumatology info cannot be used to support approval for gastroenterology indications makes much more sense now. It’s the perfect defense tactic. Though gastroenterology indications are on its label in Europe, I’m still betting the U.S. will take the cautious route and only target rheumatology indications — at least to start.
Mark your calendars for September 25, 2016. The FDA will be reviewing Amgen’s Humira ABP-501 biosimilar application. However, regardless of the FDA’s decision, there is still a high likelihood that a timely release will be delayed by the ongoing legal hassles between AbbVie and Amgen.
Last week, I noted the rising success of JAK-inhibitors, which some have speculated could steal market share away from biosimilars. This week, interleukin-17 antagonists (IL-17A) have caught my eye. In recent news, Novartis announced its IL-17A receptor Cosentryx, approved for psoriasis, had been approved for two additional indications: ankylosing spondylitis (AS) and psoriatic arthritis. Similarly, Valeant announced that the FDA has accepted for review its IL-17 receptor brodalumab injection for psoriasis.
These are both injectables, so they don’t boast a simpler formulation like Lily’s baricitinib, which can be taken orally. However, this could encroach on biosimilars’ market share. I’m going to revisit what FirstWord Pharma’s Duncan Emerton described in a recent interview: only 20 percent of those taking Humira and other anti-TNF treatments are being treated for rheumatology in the U.K. The majority suffers from gastroenterology indications. Big markets, such as the U.S., are still attempting to sort out whether a biosimilar should be used to treat all conditions specified on the reference product’s label. This could mean that anti-TNF biosimilars would only be allowed to be prescribed for rheumatology indications. The more targeted brand treatments being released in rheumatology could threaten the percentage of the population that biosimilars would be eligible to treat.
Novartis already has a reputation as being a key biosimilar player, being the first biosimilar to launch in the U.S. As such, its ranks are set to grow as the company prepares for future regulatory reviews and market releases. According to FiercePharma:
Lek, part of Novartis' Sandoz, already develops and manufactures active ingredients for biosimilars at its Biopharmaceuticals Mengeš site. But last week, Lek opened new laboratories that will allow the center to do development for the final dosage form for biosimilars, along with quality control and biopharmaceuticals technical development, the company said. The 100 new jobs boost the headcount at the facility to more than 350.
And the bolstering capacity game begins.
The FDA’s Center for Drug Evaluation and Research (CDER) plans to release 102 guidance documents this year — up from the 90 planned in 2015, Regulatory Affairs Professionals Society (RAPS) reports. Included in the agency’s 2016 plans are the three highly anticipated guidances on biosimilar interchangeability, labeling, and statistical approaches for evaluating similarity data.
This is probably not a surprise to anyone, given how highly anticipated these guidances are. The real question is going to be when in 2016 will these guidances be released for industry comment?
Regulatory Affairs Professionals Society (RAPS) reports that PhRMA and BIO have approached the FDA with more demands about how biosimilars need to be differentiated from reference products. RAPS writes:
PhRMA and BIO are calling on the FDA to include information stating that a biosimilar must not only say ‘biosimilar’ on its label but also identify the reference product. The groups even go so far as to call for biosimilar labels to describe the basis of approval for each indication with relevant data for the reference product and biosimilar.
These two organizations are taking a page from AbbVie’s book. The company has been outspoken in the past about the need for clarity in biosimilar labels. In fact, the company launched many of the same demands in the fall. I understand the need for clarity. But including all of this information in a drug label seems like overkill. It arguably will educate doctors and help them make prescription decisions, but as the market continues to grow and biosimilars prove themselves as safe and effective in the U.S., there won’t be as much need for this extensive labeling protocol. Efforts should be spent on other methods of education rather than overly technical and data-filled labels.
According to BioPharma-Reporter, Oncobiologics aims to raise $115 million to bolster its pipeline of monoclonal antibody biosimilars. The company currently has two candidates in clinical trials: ONS-3010, which is beginning enrolment this year, and ONS-1045, an Avastin biosimilar entering enrolment for Phase 3 trials. The company also has six candidates in preclinical development, with one slated to enter clinical trials this year.
I haven’t heard a whole lot about Oncobiologics’ work on biosimilars — though it does have a pretty big portfolio. The last I heard about their development program was in October when their Avastin biosimilar met the primary and secondary endpoints in the Phase 1 clinical trial. The company’s next step is to expand its capacity to meet its growing biosimilar development needs.
Nathan Monroe-Yavneh and Aron Fischer, two lawyers from Patterson Belknap Webb & Tyler LLP in their column for Lexology have revealed that Amgen has not petitioned for certiorari in regards to the Amgen v. Sandoz decision. As of January 14th, the deadline to file passed, meaning the patent dance will remain optional. However, there is a potential loophole that could be opened, should Sandoz go through with filing a cert petition against the 180-day “notice of commercial marketing provision.” Monroe-Yavneh and Fischer write:
Though Sandoz has not yet filed a petition for certiorari, it has sought an extension of the cert deadline to February 16, suggesting that it intends to file a petition next month… If Sandoz files for cert on the 180-day issue, Amgen would be able to file a conditional cross-petition under Supreme Court Rule 12.5, asking the Court to address both parties’ issues if it takes the case.
Since Amgen hasn’t already filed, it’s unlikely they would approach the Court again, according to the writers. This is good news for biosimilar makers, and frankly, for an industry that is still facing a lot of legal wrangling in the near and distant future.
In the face of biosimilars, some companies, including AbbVie, have begun investing in the development of Janus Kinase (JAK) inhibitors. While biosimilars for rheumatoid arthritis and cancers could provide more cost-effective options, these JAK inhibitors are alluring because they’re oral treatments and can treat those who don’t often have success with other drugs. Fariba Ghodsian, CIO at DAFNA Capital Management told Institutional Investor:
Obviously, AbbVie feels the fear of biosimilars for Humira, so it forces them to think about other approaches for thwarting rheumatoid arthritis competition. If these JAK inhibitors stand up to the promise they’re showing now, they might be an advantage for patients because they’re oral, so the biosimilar impact may not be as significant because they might just come up with a whole new market.
What caught my eye about the JAK inhibitors was the announcement that Eli Lilly has filed for FDA approval for its JAK1 and JAK2 inhibitor baricitinib. And this drug outperformed Humira in clinical trials for rheumatoid arthritis. Humira has plenty of other indications, but rheumatoid arthritis would be a big market to usurp for Lilly. AbbVie’s own JAK inhibitor ABT-494 recently entered Phase 3 trials. And just last week, the FTC approved the global partnership agreement between Galapagos and Gilead for filgotinib (JAK1-selective inhibitor). These drugs, if and when they’re approved, would be competing against Pfizer’s Xeljanz, which is the only JAK inhibitor on the market so far. Ghodsian makes some good and daunting points for biosimilar makers here. I don’t think these treatments would seriously quell the biosimilar market, especially when biosimilars become more common and payers become more comfortable with encouraging their use. But the notion of oral treatments is certainly an alluring treatment option compared to an injectable.
According to The Japan News, Japanese pharma companies have set their sights on developing novel, patentable treatments that bring in higher revenues. In turn, they’ve begun selling off their non-core treatment programs. This reorganization is in response to the government’s goal to increase the use of generics to 80 percent to lower medical spending. According to FiercePharmaAsia:
The most recent case was Tokyo-based Takeda Pharmaceuticals which announced that as part of its joint venture with Israel’s Teva Pharmaceuticals it would offload its off-patent and generic drugs to the joint venture to concentrate on new medicines.
By turning their attentions to novel drugs, companies like Astellas, Takeda, and Eisai stand to boost their profitability should their drugs succeed in trials and make it to market. However, this news about the country’s emphasis on generics also explains the country’s predictions for biosimilars — and indeed, could bode well for biosimilars. A few weeks ago, a press release for a report discussing Japan’s emerging role in the biosimilar industry came across my desk. A number of Japanese companies are partnered up with South Korean companies on mAb biosimilars. And, because of the uptake of filgrastim and Lantus biosimilars in 2015, Japan is expected to become a bigger player in the biosimilar world over the next five years. Biosimilars would be a decent middle ground for companies looking to boost profitability in the upcoming years. With current price reductions in Japan around 30 percent, it would be closer on the innovator side of things while still fitting with the government’s goal to lower healthcare costs.
LABIOTECH highlights the deal between Helvetic and Xbrane for Xlucane, the biosimilar version of Lucentis. Through this deal, Xbrane plans to bring the biosimilar to the Iranian market, which, unlike the U.S. and EU, has no patent protection in place for Lucentis. As the company’s CEO says:
Iran is a very interesting market with a population of 80 million, of which more than 90 percent are covered by the publicly-funded health care and we see it as an ideal first market for our lead biosimilar product Xlucane.
The author closes the article arguing that the “battle of biosimilars” is clearly not restricted to the U.S., E.U., and China. I don’t hear much about the role of biosimilars in the Middle East. But the author makes a good point that for companies looking to get their product out to the market, turning to places lacking patent protection is a good strategy.
BioPharma DIVE put together a column shortly after the new year, highlighting three of the biggest developments in 2015 to keep our eyes on in 2016. Several of these deals were in the area of new drug delivery techniques. For instance:
Prometheon Pharma is attempting to create a transdermal patch capable of passively administering everything from insulin to vaccines in safe doses. The company hopes its insulin patch could reach market by 2019, as all of the ingredients used are already designated as safe by the FDA and available for mass production.
Last year, AbbVie and Sanofi also made separate deals with Unilife for wearable injectors. In Sanofi’s case, this deal included wearables for the administration of insulin. I’m interested to see what evolutions are made in the drug delivery space, especially seeing as these changes could make the reference biologics more user-friendly and appealing to patients compared to the biosimilar version.
The Department of Health and Human Services released a document for the Federal Register announcing that the review of Celltrion’s CT-P13 will be conducted on February 9, 2016. The company aims to earn approval to treat several indications: Crohn’s disease, ulcerative colitis, arthritis, rheumatoid and psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis.
After the news last February the FDA had postponed the original hearing because it needed more information from Celltrion, this news is especially exciting. Mark your calendars! Based on its performance record in the EU to date, I’m feeling optimistic.
Two of Humira’s formulation patents are legit, the U.S. Patent Trials and Appeal Board (PTAB) ruled in response to Amgen’s recent challenge. In June, Amgen had requested the PTO review two of Humira’s patents on the grounds they shouldn’t have been granted in the first place. According to Reuters:
In declining to review the patents, the agency said “we determine, based on the petition and the accompanying evidence, that Amgen has not shown a reasonable likelihood of prevailing on any of its challenges.”
I just spoke yesterday with some experts about the use of the Inter-Partes Review process, which is what Amgen used to challenge Humira’s patents. There has been a growing number of biosimilar companies turning to this process for a quicker review. According to the experts I spoke with, the growing reliance of biosimilar makers on IPRs is one of the industry’s biggest concerns about the IPR process for the future—especially since a successful IPR can overrule decisions passed in the courts. Amgen plans to follow-up on this matter in court, so there is always the chance the courts will see differently.
The Committee for Medicinal Products for Human Use (CHMP) released a document revealing the current list of applications for medicines up for review. There were a few biosimilar surprises, including the revelation that the CHMP is currently reviewing two biosimilars for AbbVie’s Humira. The first to be accepted for review was Amgen’s ABP 501. The second, which was receive quite recently, remains a mystery. Industry grumblings have suggested it could be Sandoz’s candidate GP2017. I’ve also heard rumors it could be Samsung Bioepis’ candidate SB5, which was showing comparable efficacy and safety in a Phase 3 trial in early November, 2015.
The CHMP also recently signed up to review an application for an insulin glargine biosimilar. Rumblings across social media have suggested this could be Merck’s MK-1293. I expect we’ll learn the identities very soon, and I’ll be sure to keep you posted!
In the fiscal 2014 year, there were fewer potential pay-for-delay patent dispute settlements, the Federal Trade Commission (FTC) revealed in a new report. This lower number is in response to the FTC v. Actavis ruling, in which the Supreme Court argued a branded drug maker paying a generic competitor to settle patent litigation can violate antitrust laws. According to the FTC:
The number of these potentially anti-competitive deals has fallen significantly following the Supreme Court’s landmark antitrust decision in FTC v. Actavis in 2013. The total number of such deals filed with the FTC has dropped to 21 in FY 2014 from 29 in FY 2013, and 40 in FY 2012 prior to the Actavis ruling. The FTC staff report for FY 2014 represents the first annual snapshot of such deals following the Actavis decision.
Going from 40 deals to 21 deals in two years is an impressive drop. Though this has nothing to do with biosimilars, it suggests to me that biosimilars are entering the U.S. market at a valuable time. The Supreme Court ruling acknowledges the importance of getting generics to market as quickly as possible. Eighty percent of these 21 potential pay-for-delay settlements were resolved without having restrictions placed on the generics going to market. Decisions like these stand to reinforce a more equal playing field for generics, and hopefully biosimilars, coming to market.
Natasha Pearman, a specialist in competition law in the life sciences sector of Pinsent Masons said EU regulators are likely to start sifting through Shire and Baxalta’s early-stage pipelines to determine if any product divestments need to be made for the merger. Though they likely won’t stop there. Out-Law.com reports that:
Recent acquisitions Shire has made, including its takeover of Dyax late last year, show that Shire has "strategically been moving into the same territory as Baxalta", Pearman said. It is likely therefore that the Commission will consider all pipeline products across both companies when it comes to review the planned merger later this year.
There is still no word, and probably won’t be for a while on what will come of Baxalta’s work on biosimilars. Baxalta’s BAX 923 (adalimumab) and BAX 2200 (etanercept) biosimilars are both in Phase 3 right now. But if you look at the chart on page 15 in Shire’s investor report, there’s an awful lot of green there (signifying rare disease programs). There are very few gray boxes (other candidates). If Shire is aiming for this acquisition to build the two companies into a rare disease powerhouse, the amount of green on this chart makes me a bit nervous for the company’s future in biosimilars.
According to Regulatory Affairs Professionals Society (RAPS), the FDA is “almost certain” it will require clinical trial data in order to determine if a candidate is interchangeable — though it’s still uncertain how much data they’ll need. This data, according to a new report released by Goodwin Proctor (GP), would likely need to be gleaned from a “high-powered study,” says GP partner Rob Cerwinski. Though the guidance on interchangeability is highly anticipated, there have been few players announcing their intent to apply for interchangeability. That said, Cerwinski expects:
“Once we see some of that science worked out and it doesn’t blow the economics out of the water, [interchangeability] could very well drive biosimilar uptake in U.S.,” particularly as so many states have already established legislation requiring a biosimilar to be interchangeable for automatic substitution at the pharmacy level to occur.
I have a hard time seeing the FDA not requiring clinical data to determine interchangeability. AbbVie’s arguments that the drug should have clinical data from every indication, however, should certainly have the industry nervous. In 2015, the FDA took the middle-ground approach to naming biosimilars. I’m hoping the agency will take a similar path when determining interchangeability.
Following the news of the Mylan-Momenta biosimilar deal, Evercore ISI’s Umer Raffat has ventured that Momenta’s still-undisclosed pipeline of biosimilars contains some targets that aren’t on a lot of radars. FierceBiotech reports:
The two didn't reveal the other 5 biologics they're taking on, but Umer Raffat at Evercore ISI noted that Momenta's patent filings indicate that the remaining 5 products may include biosimilars for Rituxan, Prolia/Xgeva, Vectibix, Xolair and Campath.
Refreshing to see some possible candidates outside of the high-profile adalimumab-infliximab-etanercept biosimilar brigade.
There are also rumors this arrangement could lead Mylan to takeover Momenta. According to Ronnie Gal of Bernstein:
As a biosimilar player, the company [Mylan] had standing with potential clients, but was at a disadvantage as it came to 'scientific standing' vs. Biogen, Novartis and Pfizer. The added capabilities of Momenta puts them, in our view, at the same scientific credibility starting point as the biotech incumbents.
I’m going to keep my eyes on this possibility. Given the consolidation in the generics space, it wouldn’t surprise me to see Mylan attempting to grow its ranks after the Teva and Perrigo deals went south. I like the notion of a company known as a generics powerhouse attempting to bolster its biologics capabilities to better battle Big Pharma and Big Biotechs.
Bloomberg BNA reports that 23 patient groups have submitted a letter to the House Energy and Commerce Committee requesting hearings on biosimilars and patient safety as the biosimilar approval pathway continues to take shape. In the letter the patient groups argued in favor of more patient oversight into the biosimilar approval process to be sure patients remain protected. Bloomberg writes:
The patient groups said they believe that “greater transparency is needed surrounding the development and implementation of the biosimilars approval pathway…The complexity and uniqueness of each biologic medicine requires that FDA ensure that all biologics and biosimilars are thoroughly tested and meet the highest safety standards. Given the importance of this issue to patient safety and the impending actions by the FDA both to develop biosimilar approval standards and consider pending applications, we urge you to schedule BPCIA oversight hearings before your committee early this year and ensure patient voices are represented at such hearings.”
There have been a lot of calls for more transparency as it relates to the naming and labeling of biosimilars in an effort to make sure patients and doctors are informed and clear. For instance, the American College of Rheumatology requested the FDA pay special attention to “look-alike and sound-alike proprietary names and packaging labeling” so as to eliminate doctor/patient confusion. Since it’s the age of patient centricity and there are concerns about how patients will react to the notion of biosimilars, more transparency into the actual approval process could be a great way to build confidence and educate those who will be in line to take biosimilars.
A Momenta press release announced this new partnership which will be focused on the development, manufacture, and commercialization of Momenta’s biosimilar pipeline. There are 6 biosimilars in the company’s portfolio. I’m also drawn to this news because it reminds me of a prediction for 2016 that Bert Liang, CEO of Pfenex, voiced to BioPharma DIVE earlier this week. Liang said:
In 2016, we will see a greater degree of consolidation, with small molecule generics companies considering biosimilar investment as a growth engine that drives innovation, lowers costs and increases access.
Mylan isn’t a stranger to biosimilar development, having forged a partnership three years ago with India’s Biocon to launch three different biosimilar insulins. Similarly, the company was the first to launch a trastuzumab (Herceptin) biosimilar in India in 2014 — Mylan’s first biosimilar. Therefore, today’s news exemplifies Liang’s prediction that powerhouse generics company Mylan is well on its way to developing a larger portfolio of biosimilars.
Reuters reported today that Shire plans to acquire Baxalta for $32.5 billion. Negotiations for this deal began in July 2015, though it was originally rejected by Baxalta because of tax concerns. According to Reuters, the deal would be used to bolster Shire’s rare disease platform.
My biggest question about this is: What will this mean for Baxalta’s work in the biosimilar space?
Texas Lawyer has published an article highlighting the differences that exist between the BPCIA and Hatch-Waxman Act in terms of patent litigation for generics and biosimilar makers. Generics makers are granted 180 days of market exclusivity, and the Orange Book contains a public list of patents for the originator drug, both of which serve as incentive for generics makers to challenge weak patents and get their product to market more quickly. There are no such incentives offered biosimilar makers through the BPCIA. Rather, Texas Lawyer writes:
The BPCIA does not provide the same scope of exclusivity rewards to incentivize companies to challenge patents and open the market to biosimilar competition. A period of exclusivity is available only to the first biosimilar that obtains an interchangeability designation…If the ABLA filer simply declines to participate in the patent dance, certain conditions that could lead to a premature loss of interchangeable exclusivity can be avoided altogether. This creates another incentive for aBLA filers to opt out of the patent dance, and, accordingly, dissuades aBLA filers from challenging patents early.
This is a fresh perspective I haven’t come across yet in my readings on the remaining questions surrounding the BPCIA after Amgen v. Sandoz. The whole notion that market exclusivity is connected to interchangeability concerns me for the obvious reason that interchangeability is still unclear in the U.S. I understand the thought process here—if it’s interchangeable it’s as close as possible to the reference drug, just as a small molecule generic is with its originator. But getting the product to market as early as possible is important for the company to be able to profit from biosimilars and remain competitive. Limiting exclusivity to interchangeable biosimilars seems to be just another way to keep the market from moving forward.
Under the BPCIA, biologics are granted 12 years of market exclusivity before a biosimilar can enter the market. As Regulatory Affairs Professionals Society (RAPS) writes however, this requirement has been challenged in the recent Amgen v. Apotex case. In December, a judge in Florida ruled that the 180-day delay to market was mandatory, even though Apotex claimed this period was not mandatory because the company had previously engaged in the patent dance with Amgen. The Biosimilars Council has just come out in agreement with Apotex, stating:
By its very definition and as Congress intended, the 12-year exclusivity period should operate to prevent a biosimilar’s launch for only that length of time, and no more…This Court’s extension of its (erroneous) decision in Amgen v. Sandoz would have the additional effect of disincentivizing use of the section 351(l) patent dispute resolution provisions altogether – another consequence Congress could not have intended.
I’m in agreement with the Biosimilars Council here — eliminating the six-month waiting period could be a good incentive for companies to engage in the patent dance now that it is not mandatory. For a good summary of the case so far, check out this article from Patterson Belknap Webb & Tyler LLP.
BioPharma-Reporter published this gem of an article today discussing some of the things we should keep in mind moving into 2016. In an interview, Andrew Williams, a partner with McDonnell Boehnen Hulbert &Berghoff LLP, states that one question remaining for biosimilar makers following the FDA’s approval of Zarxio is:
How much data the FDA would require to establish the ‘no clinically meaningful difference’ standard for 351 (k) biosimilar applications. Sandoz had already had extensive experience with this product because it received approval to market this drug in Europe in 2009. However, it is currently unclear to what extent this experience expedited the review of the U.S. application. It remains to be seen what level of scrutiny the FDA will apply to biosimilar applications that do not have the data that a corresponding approval in another jurisdiction provides.
Williams raises some good points here. I expect the biosimilars up for approval in the U.S. that haven’t been on the market in Europe for long (which are quite a few of them) will definitely impact the length of time the FDA takes to review each application. I’m especially interested in Amgen’s submission to both the FDA and the EMA. These two agencies are often releasing reports about how they compare to each other in terms of drug approvals and time to market for new drugs. I’m curious if that healthy competition will impact the speed at which the Amgen Humira biosimilar application is reviewed.
Stacie Ropka, an IP attorney from Axinn Veltrop & Harkrider, discusses some of the challenges facing biosimilar makers from a regulatory standpoint in the U.S. Ropka tells BioPharma-Reporter that one of the biggest challenges for a company is “coming up with the type of assays the FDA feels support a finding of biosimilarity.” The article states:
Now as the FDA is beginning to see more biosimilars they are developing a clearer understanding about what they want to see in order to demonstrate biosimilarity. ‘Right now they don’t have a lot of data in front of them to start forming additional conclusions and that why they still say it’s a case by case basis,’ explained Ropka, ‘and that’s why it’s important to meet with them.’
Meeting with a regulatory agency early on in the development process is rising in popularity. Earlier this year, the EMA saw 77 percent of those applying for biosimilar approvals in the EU come to the regulatory body for early scientific advice. I have no doubts that this trend will also be observed in the U.S. as more players enter into biosimilar development.
The Journal Of Crohn’s And Colitis published a preliminary observation for a trial in which children with irritable bowel syndrome (IBD) were switched between Remicade and the biosimilar Remsima. The doctors came to this conclusion:
Switching from IFX originator to its biosimilar seems to be a safe option in children with Crohn’s Disease. Biosimilars after switch showed to be equally effective as its originator.
AbbVie has filed a Citizen’s Petition urging the FDA to take its time on the interchangeability guidance. The company says it believes science will be able to prove biosimilars can be interchangeable. However, at this point the company voices concern about whether the science is at the level it should be to determine interchangeability. Bioworld writes:
AbbVie's petition cited a number of professional and regulatory guidelines that warn against switching or alternating between highly similar biologics because of the immunogenicity risks...AbbVie's petition also asked the FDA to ensure that interchangeability candidates meet the Public Health Services Act's "Safety Standards for Determining Interchangeability" for each condition of use for which the reference product is licensed, regardless of whether the sponsor is seeking approval for the entire reference label.
I was recently reviewing Evaluate Pharma’s 2016 Preview, which briefly discussed the obstacles standing in the way of biosimilars coming to market. We’ve just found one — an analyst from Bernstein predicted citizens petitions would be one of methods used to slow biosimilar entry.
Law360 says there are four cases currently awaiting final rulings. These include Janssen Biotech v. Celltrion; Amgen v. Apotex; and Amgen v. Hospira. The article also references the Amgen v. Sandoz case, granting reference product sponsors an additional six months of exclusivity. As James Hurst, partner at Kirkland & Ellis says, this exclusivity period can be problematic because:
‘It can make consumers wait for six months after FDA approval for potentially nothing.’ He said that period is set aside essentially for patent litigation, which isn’t always a concern.
Not quite sure what Hurst means here when he says patent litigation isn't a concern. Perhaps he means that the litigation could come out in favor of the biosimilar company in the end, therefore rendering this six-month period void? I have a hard time believing that a biosimilar company won't be faced with nor be concerned about patent litigation.
According to Quintiles, Asian companies will have a better chance of getting their biosimilars approved in Western Markets because of the size of their pipelines. The Business Standard quotes Quintiles Asia’s Dr. Charu Manaktala saying:
We are beginning to see a change in the development strategy for some of the Asian customers. Instead of the earlier approach of developing products for local/regional markets followed by the Western markets, some Asian companies are now planning to develop products for global markets right from the outset.
I’m not entirely sure this alone will give them the advantage. Now that the U.S. market is open to biosimilars, there are a number of companies that have initiated global clinical studies to ensure they have the appropriate data for global regulatory submissions. I’m thinking particularly of Amgen, which recently filed for its Humira biosimilar in the U.S. and the E.U.
Aurobindo Pharma is currently in talks with an unknown drug company to acquire four biosimilar products, Livemint reports. The candidates in question are trastuzumab, bevacizumab, infliximab, and etanercept. According to Livemint,
The deal will pit the Hyderabad-based drug maker against the likes of industry behemoth Biocon and others, such as Dr. Reddy’s Laboratories and Intas Pharmaceuticals, which are looking to launch biosimilars for Europe and other highly regulated markets.
I’ve heard a lot about Biocon and the role it will play in the biosimilar market. The candidates Aurobindo is looking at are all currently in clinical trials, which Livemint says puts the company ahead of some other rivals in Europe. I’m predicting there will be more focus in the New Year on Indian companies and what looks to be their race to market with biosimilars.
According to Regulatory Affairs Professionals Society (RAPS), the FDA has launched a public meeting to begin establishing the second Biosimilar User Fee Act (BsUFA) programs. The Act faces expiration in September 2017, and between now and then, the FDA has to determine the revenue needed to ensure the agency will be staffed to meet with sponsors and review biosimilar applications. David Gaugh, VP of the Generic Pharmaceutical Association (GPhA) says:
To date, 8 BLAs [biologics license applications] have been announced as submitted to FDA, and the action date for five of these submissions has passed. We only know the review outcome and timing for two of these five. And for the two, FDA has completed their review within the 10-month goal — Sandoz’s filgrastim with an approval and Pfizer’s epoetin alfa with a complete response letter. Of the remaining three, we do not have public information concerning their status.
I’m struck by the final sentence here. RAPS mentions that the FDA has been meeting more regularly early on in the drug development cycle with companies. But it does still seem as though there is a striking lack of transparency when it comes to the review of biosimilar applications. The department still has a lot of growth to undergo, and Janet Woodcock did express the industry’s concern about making sure the science is “bulletproof.” But especially as the industry takes shape in the U.S., I’d think more transparency into this review process and why some of these applications have taken so long to review would be eye-opening for industry players.
Generics and Biosimilars Initiative Journal (GaBI) published a survey which revealed the perspectives on biosimilars of physicians in Argentina, Brazil, Colombia, and Mexico. The whole article is worth a read, but in terms of education, the survey revealed that:
Nearly a third of prescribers in Argentina (29 percent) claimed to have learned about biosimilars through clinical trial participation, whereas just over a tenth of prescribers in Brazil (12 percent) reported learning though clinical trial participation. A relatively high number of prescribers in Brazil (60 percent) reported learning by self-study, compared with only 39 percent in Argentina. Over half the prescribers in Argentina (53 percent) claimed they became familiar with biosimilars with the help of (potentially biased) information from the companies that make biosimilars.
The drastic differences in the ways physicians have learned about biosimilars seems indicative of the fragmented nature of the entire biosimilar market from country to country. I found the fact that 60 percent of doctors had learned about biosimilars through self-study to be particularly interesting. The fact that 53 percent in Argentina have gotten information through biosimilar companies also suggests that the educational strategies at play in that country are clearly working. However, physicians in all the countries said they’d prefer to learn about biosimilars through national and international medical conferences. Makes me wonder if this is indicative of the way educational materials have been presented, or if the information contained in this outreach is the most useful information to encourage physicians to turn to biosimilars.
Basaglar, a biosimilar version of Sanofi’s Lantus, won approval as a “follow-on” biologic from the FDA. The product will hit the market starting in December 2016, says BioPharma-Reporter. While the drug is currently approved in Europe as a biosimilar known as Abasria, Boehringer-Ingelheim, told BioPharma-Reporter that:
Lantus has been approved by the FDA [in 2000], not as a biopharmaceutical, but as a new chemical entity (NCE). Therefore, the approval process for our product with Lilly could not follow the U.S. biosimilars-specific 351(k) pathway but rather the 505 (b) (2) pathway.
It’s kind of unfortunate that it doesn’t count as a biosimilar in the U.S. But considering some of the issues that have yet to be decided, including biosimilar labeling, the company claims to be grateful that the product won’t “suffer from a lack of clarity in the labelling of biosimilars.” This is also great news for the growing number of diabetes patients in the U.S. who hopefully won’t be facing any delays in receiving the generic insulin due to any lingering lack of clarity in the biosimilar space next year.
The Swedish Government has announced plans to set aside $37 million in funding for protein, research, method development, and biologic production over the next eight years, BioPharma-Reporter announced. The country currently houses facilities owned by Pfizer, Octapharma, and Cobra. AstraZeneca also has biomanufacturing investments in Sweden. According to the Minister for Higher Education and Research, Helene Hellmark Knutsson:
The Government is taking steps to strengthen Swedish research and innovation. This investment in next generation biologics is part of efforts to make Sweden a leading research nation.
Enterprise and Innovation Minister, Mikael Damberg, adds:
Collaboration between academia and industry, and between small and large companies, is essential to managing health-related societal challenges.
It sounds like this investment is earmarked primarily toward new biologics. But I’m interested to see what impact this investment will have on the biosimilar environment in the country as well. After all, Pfizer, one of the newest players in the biosimilar space following its acquisition of Hospira, manufactured its Genotropin (somatropin) growth hormone therapy in Sweden — a biologic that is currently being developed as a biosimilar by Pfenex.
A Pharmaceutical Processing article has compiled a list of the top industry trends that will impact the development of injectables in 2016. While Quality by Design (QbD), supply chain risks, and the growing interest in combination products impacted injectables in 2015, Karen Flynn, president of pharmaceutical packaging systems at West Pharmaceutical Services, homes in on three emerging trends: Flexible manufacturing, continuous v. batch manufacturing, and biosimilars.
With several companies competing for the same biosimilar, the mechanism of administration can be a key differentiator. For injectable biosimilars currently in the pipeline, it will be important to examine drug delivery options that can improve the patient experience while ensuring, when possible, a delivery format that patients are currently familiar and comfortable with.
Makes sense, seeing as one of AbbVie’s strategies to fight biosimilars is to make the administration method less painful.
According to Bidness Etc., Amgen has arranged to reacquire sales rights to Prolia, XGeva, and Vectibix in China, Brazil, South Korea, Israel, Hong Kong, Taiwan, Singapore, Colombia, and Thailand.
According to Amgen, the three drugs combined generated sales of $111 million for GSK in 2014 under the licensing deal. For Amgen, the drugs generated $2.75 billion last year, according to Bloomberg data.
These drugs are targeting osteoporosis, skeletal conditions, and advanced colorectal cancer. Amgen’s been in the spotlight a lot lately, what with its recent submission for its Humira biosimilar, its triumph against Apotex, and not this deal. Looks like the company has a well-rounded approach for facing the biosimilar challenge.
The U.S. District Court for the Southern District of Florida has ruled that Apotex will need to delay the launch of its Neulasta biosimilar for 180 days following regulatory approval, Bloomberg BNA reports. This decision is one step toward answering a lingering question from the ruling of Amgen v. Sandoz before the U.S. Court of Appeals for the Federal Circuit. Goodwin Proctor’s Nicholas Mitrokostas told Bloomberg:
If the 180-day notice of commercial marketing is mandatory even when manufacturing and other disclosures have been provided by a biosimilar applicant under [45 U.S.C.] Section 262(l)(2), as the district court has now found in Apotex, then one consequence could be a reduced incentive on the part of future biosimilar applicants to engage in the disclosure of information.
An interesting turn of events here to take note of. Apotex had provided a copy of the Biologics License Application (BLA) to Amgen, but will still be responsible for holding its product from the market for 180 days. Mitrokostas says there will likely be an appeal.
Healio features an article by a physician, John Sweetenham, who discusses his uncertainty over biosimilars. His discussion of extrapolation is what struck my eye. Sweetenham states:
If the molecule is highly similar to the original compound and there are clinical data for one disease entity confirming its efficacy, why not extrapolate these data into other conditions? The fact is, we do it all the time. Many of us, for example, give maintenance rituximab to patients with follicular lymphoma after bendamustine rituximab induction… If randomized clinical trials were required for these agents for every indication, they would probably never be done. Apart from the expense of these studies, how many patients would sign up for a randomized study in which they are being offered, at best, the same outcome on both arms?
Sweetenham makes a good point here. It’s no secret recruitment is a difficult endeavor for every indication. Requiring companies to gain approval for all indications would only make recruitment a more strenuous task and certainly delay the growth of the market.
An article in Bloomberg discusses how the current biosimilar market is aligning with the Federal Trade Commission’s (FTC’s) predictions from six years ago. FTC attorney advisor Elizabeth Ann Jex at the ABA Health Law Summit said:
The FTC had also predicted in 2009 that competition between a reference product (RP) and a biosimilar would resemble brand-to-brand competition more than the dynamics of brand versus generic drugs; that there would likely be only two to three biosimilars per RP seeking FDA approval; and that the lack of automatic substitution between biosimilars and an RP would slow the rate at which a biosimilar could acquire market share. ‘Sadly, what we wrote in 2009 is coming to bear,’ Jex said.
The notion that competition is going to resemble brand-to-brand competition was really spot on. The debates over naming, labeling, and interchangeability seem indicative of the industry’s confusion over where biosimilars fit into the innovation paradigm. The FDA’s guidance on naming, for instance, suggests that biosimilars have crossed the line from copy to unique player on the market.
An article by Naomi Pierce of K&L Gates, featured on Lexology, discusses how the Court of Appeal decision on the Commonwealth of Australia v Sanofi case looks to benefit biosimilar makers in Australia. According to Pierce:
Product sponsors will have good reason to pause before seeking interlocutory relief on vulnerable patents in Australia; generic/biosimilar manufacturers may be afforded greater opportunities to launch “at risk”, without interlocutory prohibitions; and the Commonwealth (and the public) will be compensated for delays to competition due to interlocutory injunctions which are ultimately overturned.
This is good news for Australia’s small generics industry, which has been looking to draw biosimilar makers into the country to bolster the existing market.
According to a new study discussed in Medscape, rituximab combined with chemo has proven beneficial in improving survival rates in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). According to David Steensma, an expert from the Dana Farber Cancer Institute:
This is a very curable malignancy in children, but it has poor outcomes in adults. These new results will immediately change clinical practice.
If that’s the case, this will widen the scope of indications for biosimilars of rituximab.
Business Insider published a feature on biosimilars and the impact they could have on drug costs and on biologics companies. The part that caught my attention was the interview with an expert from Amgen’s biosimilar unit. Business Inside writes:
Geoffrey Eich, a spokesman for Amgen Biosimilars, told Business Insider that the biosimilar competition Amgen would face from Zarxio inspired them to launch its own biosimilar development. Amgen had the experience of working with branded biologic drugs, so why not make biosimilars as well? ‘Competition is a good thing,’ he said. ‘Biotech has to think about having an eye toward the end of a drug's life cycle to reinvest in new medicine.’
I’ve always been curious about how reference biologic makers, such as Amgen, go about negotiating the conflicting interests between bringing innovator biologics and biosimilars to market. In an interview I did with Biogen, the company also referenced turning to biosimilars because of the company’s skills with biologics. I like what Eich says here. When I think of a drug’s development and lifecycle, I don’t loop patent expiration in there. It’s interesting to think about how a biologic’s patent expiration actually becomes a key moment in the life cycle of a biosimilar.
After encountering safety risks in the development of its long-acting diabetes treatment candidate, Eli Lilly has set itself up to be a bigger player in the biosimilar insulin space. According to FiercePharma:
When Lilly held off work on peglispro earlier in the year, Bernstein analyst Tim Anderson was one who saw some benefit for Lilly's biosimilar effort in the move. He figured by not having to focus peglispro in the mix, Lilly could put more muscle into marketing the Lantus biosimilar and discount it more deeply without the worry of cannibalizing sales from its own long-acting insulin.
This could be a blessing in disguise for Lilly and its burgeoning biosimilar business. In a recent interview, the expert, employed by a leading biotech engaged in biosimilar development, expressed the importance of marketing a biosimilar. Thinking beyond the technical, scientific development is just as important for the success of the product. Similarly, as there are so few (I’ve only come across one) other companies developing biosimilars for insulin, Lilly stands to gain some significant market share here — especially if they’re boasting steeper discounts. (Though how "deep" could we really be talking, given the lack of competition on the market right now?)
According to Family Practice News, in a follow-up trial, the effects of etanercept and adalimumab in treating pediatric psoriasis have been deemed “encouraging.”
‘This is the largest and longest follow-up of any biologic in children and adolescents to date. I think it’s encouraging data and should be reassuring to those of us who are managing this important population of pediatric patients in our conversations with parents and families,’ said Dr. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
This bodes well for the use of biosimilars in treating pediatric patients.
A recent study published in the American Journal of Clinical Oncology has uncovered a potential pattern in how pharma companies have used the Orphan Drug Act. Some pharma companies have their drug reviewed by the FDA for a narrow indication, earning orphan drug approval and the grants, tax incentives, and exclusive marketing rights that come with it. However, when released on the market, the drug is used to treat off-label, broader, non-orphan indications. For example, CNBC writes:
Rituxan (rituximab), which is made by Roche and was initially FDA approved for use in the treatment of follicular non-Hodgkin's lymphoma, is the No. 1 selling medication approved as an orphan drug. ‘It is currently used to treat a wide variety of conditions, ranks as the 12th all-time bestselling medication in the United States, and generated over $3.7 billion in U.S. sales in 2014,’ the report states.
What struck me most when looking at the list of blockbuster drugs with orphan status is that all of them, with the exception of two, are biologics that are currently or will soon be facing biosimilar competition: Humira, Avastin, Herceptin, Rituxan, and Remicade. The article doesn’t specifically address biosimilars, but when it comes to future biologics that will someday face biosimilar competition, it sounds like the scope of diseases an orphan drug can treat will need to remain quite narrow. This will naturally affect the patient populations that qualify for a biosimilar.
Just a week or so after submitting its application to the U.S. for its Humira biosimilar, Amgen has submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA).
Amgen believes this submission is the first adalimumab biosimilar application submitted to the EMA and represents Amgen's first biosimilar to be submitted for approval in the European Union.
Seems to me like the choice to submit to the U.S. first was definitely a strategy to make a splash in the market. After all the buzz about Humira’s extensive patent coverage and yearly sales, this is certainly a milestone for Amgen as it strives to be recognized in the biosimilar space.
In an article on JDSupra Business Advisor, Irena Royzman and Jacob Siegel of Patterson Belknap Webb & Tyler discuss the industry’s response to the FDA’s draft guidance on naming. Numerous health care and biologics companies called for distinguishable nonproprietary names, while those on the biosimilars side are still skeptical about the impact differentiating biologics/biosimilars names will have on biosimilar uptake. Overall, however, the two sides found some common ground:
Since interchangeable products will likely first be approved as biosimilars, both camps advocated keeping the initial biosimilar name rather than changing it after approval as an interchangeable product. As a result of this unified view, FDA is likely to expand the naming approach it ultimately adopts for biosimilars to interchangeable products.
I wasn’t aware there was talk about giving biosimilars that were deemed interchangeable a separate name. I was hesitant as it is about the naming solution the FDA came up with. But to add yet another level to distinguish biosimilars — not only from the reference product but other biosimilars on the market — would, frankly, be overkill.
Duncan Emerton of FirstWord Pharma has put together a Q&A exploring the recent progress of the anti-TNF pipeline. He focuses on the prospective approval of Benepali in Europe, as well as Amgen’s bold and surprising decision to file its Humira biosimilar application in the U.S. rather than in Europe — despite the large number of patents still protecting Humira in the States. According to Emerton:
Potential reasons are manifold, but are likely to focus on Amgen’s confidence that it has the legal muscle to challenge and potentially overturn some of AbbVie’s key Humira patents. CEO Bob Bradway was quoted as saying "we recognize that there is intellectual property here that needs to be respected, but we will continue to advance our molecule and continue to assess the intellectual property that's in place," suggesting legal challenges are likely to form a key part of Amgen's strategy.
And thus begins the legal wrangling. AbbVie is confident its patents will keep away competition until at least 2020. Part of me wonders if this move goes beyond Amgen’s desire to knock out some of these patents, though. Because it was such a confident move, it could have something to do with Amgen’s attempt to stake its claim and assert dominance in the biosimilar space, especially as the first biosimilar in the U.S. to hit the market was a competitor of an Amgen biologic. It also fits with the well-rounded pipeline awaiting FDA approval currently, including biosimilars for Remicade, Epogen, Neulasta, and Procrit. To be the first to start gaining market share in the U.S. for Humira would be a lofty status to attain for the company that stands to face the largest amount of competition to date.
According to Pharmaphorum, at the Ethical Medicines Industry Group (EMIG) conference, Macolm Qualie, pharmacy lead, specialized services at NHS England, said the NHS is working to establish a system of incentives to encourage doctors to switch patients to biosimilars.
Qualie says commissioners could agree to a 'year of care' tariff at a price which provides savings against the originator product but would also allow Trusts 'a gain share opportunity' – a chance to hold on to any savings made from the switch to a biosimilar. The level of annual payment would be reviewed as more biosimilars are used, but this could translate into savings of thousands of pounds for each patient treated. This would give the Trusts a major incentive to switch and translate into system-wide savings of millions.
In an interview I had recently, the expert mentioned the use of gain share models and how the countries in Europe were watching each other, especially where gain share models were concerned. I’ve always wondered about the need for incentives to switch patients to biosimilars — especially in the earlier, more uncertain stages of the market. I have a feeling however, that the older the market becomes, much like the small molecule generics market, doctors will end up prescribing biosimilars — regardless of incentives.
Celltrion was recently featured in a Nikkei Asian Review article. The company has been named one of two “breakout” drug makers that stand to put South Korea on the map for drug development innovation — especially in the biosimilars realm.
New-drug development is a tough field. Not even 1 in 10,000 attempts at commercialization actually pan out, some say. ‘That was not the business for us,’ Celltrion CEO Kim Hyoung-ki said. But the founders' automaking experience helped guide them through the process of mass-producing drugs. South Korea's chipmaking industry provided much of the technology used to build the clean rooms necessary for biosimilars development.
This was an interesting profile of Celltrion’s current work in South Korea, especially seeing the ways other industry innovations can be used to support biosimilar development.
According to a recent study carried out by the American College of Physicians and published in the Annals of Internal Medicine, there is still plenty of room for growth in the generics industry. According to The Washington Post, many doctors continue to prescribe the brand name drug because of patient requests, quality concerns, or because doctors refer to drugs by their brand names. Interestingly enough, however, generics were found to be a potential answer to adherence difficulties. As the study detailed:
Prescriptions for brand-name medications are almost twice as likely as those for generic therapies to be 'abandoned' (that is, never picked up after being filled)… Thus, greater use of generic drugs could result in long-term adherence to essential therapies.
I found this interesting and relatively surprising. There was no explanation for why this might be, but my primary guess would be cost. I’m curious if this logic could be applied to the biosimilars realm — especially since one of reference product sponsors’ main defenses is arguing that their brands have a reputation that will be hard to replace.
Brazil currently has one of the world’s 20 biosimilar medicines following the approval of Eurofarma’s Fiprima, a biosimilar of Amgen’s filgrastim, by Brazil’s regulator ANVISA, says BioPharma-Reporter. According to Eurofarma’s Vanda Magalhães, this biosimilar was developed in Brazil using domestic technology and expects to produce 360,000 annual doses beginning in early 2016. Magalhães says:
‘We started the project in 2006. We developed and executed all phases of the procedure, from the construction of clone, process development, to analytical methodology. Just to have an idea of the importance of this advance, there are only 20 biosimilar drugs in the world, one in the United States and another 19 throughout Europe.’ South Korean Celltrion’s biosimilar Remsima was approved by ANVISA this year, but Eurofarma claims its biosimilar is the first to be developed domestically.
From this story, it would seem biosimilars are no longer just the answer to high drug costs; the development and manufacturing of them is also becoming a source of pride and a part of a nation’s identity.
Marvel LifeSciences’ biosimilar of Eli Lilly’s Humilin S. insulin was not recommended for approval by the EMA’s Committee for Medicinal Products for Human Use (CHMP). According to Medscape, this biosimilar, known as Solumev, was rejected because:
The CHMP was concerned that the company did not define the product’s manufacturing process in sufficient detail to warrant a positive recommendation…The company had presented clinical studies in healthy people and in those with type 1 and type 2 diabetes…But the CHMP said that there was insufficient evidence showing that the product used in those studies was representative of the batches intended for the market and that its quality was comparable to that of Humilin S.
I haven’t heard a whole lot about insulin biosimilars being submitted for review or being approved for the market, apart from Lily’s and Boehringer Ingelheim’s insulin glargine biosimilar. So this news stuck out to me. I was just reading the other day about a team of scientists that is working on creating biosimilar insulin from E. coli. in the hopes their research will someday be picked up by a pharma company looking to develop and commercialize it as a biosimilar. They also plan to document their process. One of the scientists quoted in the article argues that the process of making insulin is not the major hurdle facing companies—it’s the approval process and the upfront manufacturing costs. I’m curious about the effects, if any, crowdsourcing research might have on the development of biosimilars for products such as insulin for companies developing biosimilars in the future.
Korea IT Times reports that Samsung Bioepsis is dropping $1 trillion on what will be the world’s largest contract manufacturing plan in Songdo, Incheon. This news follows the company’s announcement that the CHMP has given a nod to its application for a biosimilar of Enbrel. As Korea IT Times reports:
In response to the rising demand, Samsung Biologics, the largest shareholder to Samsung Bioepis with a 90.3-percent stake, will build a third plant with an annual capacity of 180,000 liters. Currently the company runs two plants in Songdo, each with an annual capacity of 30,000 liters and 150,000 liters. Including the third one which will have a 180,000-liter capacity, the company will be able to produce 360,000 liters of the biosimilar drug in a year.
Not only will Korea have the largest numbers of ongoing biosimilar trials and pipeline targets, it’s now going to boast this facility as well. I’m excited to see what role the country plays in the future of the market.
At the recent BIO IP Counsels Committee Conference, experts discussed the recent decision by the U.S. Court of Appeals for the Federal Circuit in Amgen v. Sandoz. As Bloomberg BNA reports, many panelists have chosen the word “fractured” to describe the recent statute. It will serve as a major frustration for companies as they look to launch biosimilars and protect their brand biologics from generic competition. As Lisa Barons Pensabene, head of life sciences litigation at O’Melveny & Myers, describes the future as:
A BPCIA-ish world, with applicants picking pieces of BPCIA to hand over, turning over lists of patents to the RPS and saying, ‘Go on and sue me for infringement based on the list if you can, but we have met most of the requirements of the BPCIA and therefore don't have to give you 180-days notice.' This has some appeal. An RPS will have a list of patents the biosimilar could infringe, and if a patent is not on list, the RPS can never assert infringement of that patent.
Interesting prediction to note here.
The Committee for Medicinal Products for Human Use (CHMP) gave a thumbs up to Samsung Bioepis’ Benepali, a biosimilar of Enbrel. The drug application is now being reviewed for final approval by the European Commission. If granted marketing authorization, this dynamic duo would be the first company to launch a biosimilar of Enbrel on the European market, FiercePharma reports.
This certainly bodes well for this partnership and their emerging biosimilar business. If you’re interested in learning more about Biogen’s work in the space, I recently had an interview with Alpna Seth of Biogen.
Despite the challenge biosimilars pose to Humira, AbbVie has announced it does not plan to branch into its own biosimilar development endeavors. According to Pharmafile, Perry Siatis, CP of biologics strategic development at AbbVie said at the recent FT Global Pharmaceutical and Biotechnology conference:
We believe in developing and bringing to market innovative biologics and will continue to do so. Because of the risk that comes with switching, we would not support a switching strategy, and at the moment, we do not believe that regulators have the policies in place to be able to manage that risk.
Good to know, though this probably shouldn’t be a surprise, given the company’s continued work on gaining new indications and improving the formulation of Humira. The company seems more devoted to its innovator drugs rather than competing in the generics’ space.
Epirus is well on its way to filing for approval of its infliximab biosimilar in Canada, the EU, and the U.S. in 2017, according to BioPharma-Reporter. BOW015 was previously launched in 2014 in India as Infimab. While Hospira and Celltrion have already launched infliximab biosimilars, and more competition is coming from Samsung Bioepis and Amgen, Epirus is still confident the market will still provide market share. A spokesperson told BioPharma-Reporter:
While there will be competition, there will also be a large opportunity for biosimilars. Currently Remicade sales are estimated to be just shy of $9 billion. Assuming around a 40 percent price discount and significant biosimilar penetration overtime, we estimate a biosimilar market opportunity of around 3 billion…We do not anticipate the discounts to drop to a level where it would be too low to compete.
I found this perspective interesting because I’ve been coming across a number of industry members saying they do not see the market being a success should biosimilars become a commodity. Despite the large number of competitors that could threaten market share, it seems that Epirus is not concerned about competition leading to future commoditization.
Spain Removes Market Barriers To Biosimilars (11.17.15)
BioPharma-Reporter has announced that Spain will no longer be capping the prices of brand name pharmaceuticals/biologics. Originally, the country required drug companies to charge the same prices as the generic for off-patent branded meds. The European Generic and Biosimilar Medicines Association (EGA) stated:
This policy is detrimental to the long-term ability of the generic medicines industry to increase patients’ access and provide savings to Spanish payers, as it removes all incentives for physicians to prescribe, pharmacists to dispense, or patients to ask for a generic medicine.
No kidding. This policy is a biosimilar’s nightmare. Glad to see the EGA and the Spanish Generic Medicines Association (AESEG) taking steps toward eliminating barriers to biosimilar uptake.
Reference product sponsors (RPSs) facing patent expirations are looking for new ways to save their brand products from biosimilar competition, the Business Standard reports. There are a number of ways companies could go about doing this, many of which probably will sound familiar. Though there were a few in particular that had relevance to the current market, including:
Introducing new brands with similar efficacies for the same indications as the existing brand and build a portfolio
I thought we were moving out of the “Me Too” drug era? Could the looming threat of biosimilars bring it back?
Reposition the brand for alternative indications for the same molecule: Apply for a further patent to increase the brand’s patent lifespan.
Humira is a prime example of this. Though, still available to biosimilar makers at present is the inter partes review (IPR) process. It’s not going to necessarily eliminate every necessary patent. But quality of patent is going to need to be the real focus for RPSs to protect their brand.
Introduction of novel formulation of the same brand; maybe a farfetched proposition because most of these are injectable.
It’s not farfetched for Humira, which recently won EU approval for a new formulation. My bet is this is going to be the most popular method for encouraging brand loyalty and deterring competition.
In her Forbes column, Grace-Marie Turner argues against the most recent decision The Centers For Medicare and Medicaid Services (CMS) made regarding biosimilar payment codes. All biosimilars for a specific reference product will be categorized in the same category, just as small molecule generics are. Turner argues against this decision for a number of reasons, including:
Thwarting safety tracking: If there are adverse side effects with one biosimilar, it could be difficult to identify the manufacturer since all will have the same payment code.
(Wasn’t this the reason that the suffix was added to each biosimilar name?)
Compromising patient care: Since doctors will be reimbursed at one price under the CMS rule no matter which biosimilar they pick, they may be financially forced to pick the cheapest version, regardless of whether their patient may already be stable and doing well on a different biosimilar.
If this were to be the case, this would throw a wrench in a company’s market share. Every company would want to be the cheapest to gain the greatest market share — which leads to Turner’s final point:
Deterring competition: The CMS rule for blended codes would pervert the economics by creating a race to the bottom pricing dynamic — akin to the generic drug market.
There it is: commoditization. Seems that is one of the biggest concerns keeping the industry up at night thus far in the biosimilar age.
According to BioPharma-Reporter, the U.K. biopharma industry is facing a dearth of skilled manufacturing workers. The Association of the British Pharmaceutical Industry (ABPI) and the Medicines Manufacturing Industry Partnership (MMIP) recently conducted a survey which highlighted the need for more skilled employees in quality operations. BioPharma-Reporter writes:
Within quality operations, validation skills were identified as a major gap. The largest problems occurred in emerging areas, such as validation for Quality by Design programs… Analytics training is seen as important for biologics manufacture for data analysis, and respondents were concerned about meeting future needs as this sector grows.
As the European biosimilar market keeps growing as well, skilled employees in quality and data analysis will be key, though this is certainly a question plaguing a number of markets, including the U.S. My colleague at Outsourced Pharma wrote an interesting piece on this very topic. Could be a big trend to keep tabs on, as it could stall growth of the global biosimilar market and hold back certain countries from becoming leaders in the space.
South Korea’s Celltrion Powers Ahead With Rituximab Biosimilar (11.12.15)
Biosimilar News reports that Celltrion has submitted an application to the European Medicines Agency (EMA) for its rituximab biosimilar (CT-P10).
Although the application has been made, it is still unclear which indications Celltrion is seeking. There are rumors that the company has made the application only for the rheumatoid arthritis(RA) indication, which is still a very small portion of the whole rituximab business.
Celltrion is definitely one of the companies to be watching right now, given so many other big players’ inabilities to master the rituximab biosimilar. There’s still a chance other companies will be able to get their foot in the door, especially if Celltrion is only going for the RA indication. This is where rulings on extrapolation could come in handy to help other companies determine market share.
The American College of Rheumatology recently released its 2015 guidelines for the treatment of rheumatoid arthritis (RA) — but this update excludes any reference to the use of biosimilars. According to Medscape, when the literature review was conducted in the fall of 2014, there weren’t any biosimilars approved in the U.S. However, as Medscape notes, Seth Ginsberg, the cofounder of CreakyJoints, an online community of arthritis patients, said:
He pushed without success for the committee to make recommendations on biosimilars. There might not be a lot of data that can be used to address these subjects, but the committee made recommendations without strong evidence on other topics, Ginsberg pointed out. In fact 77 percent of recommendations in the guidelines are ‘conditional’ because of weak evidence.
I can only assume that biosimilars will appear in these guidelines in the near future. However, it’s situations like this that are particularly frustrating given the fact that these treatments have been used for ten years in Europe without causing serious adverse effects. I find it telling that, in a country where there is little education on biosimilars, patients are pushing for this kind of treatment to be included in the guidelines.
According to Politico, France is currently attempting to alter drug labels to include a new chart and the phrase “made in Europe” in order to bolster transparency about a drug’s origins. As Politico explains:
The pictogram…would be a rectangle divided into four parts, each identifying a specific stage of drug manufacturing: “Excipients”, “Active substance”, “Production”, and “Packaging.” Each section would have the word “Europe” in white on a blue background if that stage of manufacturing, production, or packaging took place in the EU or in the European Free Trade Association. Otherwise, it would bear a black cross.
The article focuses specifically on the impact this labeling change would have on the nation’s trust for generic medicines, especially given some of the recent quality issues related to India. One expert stated that “the idea was to put a label on quality.” Given comments to the recent FDA naming guidance calling for more meaningful suffixes — preferably ones that are abbreviations of the manufacturer — for the sake of transparency and traceability, I’m curious about whether we’ll ever see a similar proposal here in the U.S. and how that could be used to benefit — or harm — biosimilar products.
The Pharma Letter reports that the European Biosimilar Medicines Group was a participant in this year’s DIA conference. A major topic of discussion was biosimilar medicines labeling, which currently involves including the Summary of Product Characteristics (SmPC) describing its medical use so that the label is consistent with that of the reference product. According to Suzette Kox, director international EBG:
The EU naming policy is science-based and 10 years of compelling EMA data demonstrates that traceability by brand name is totally effective. The proliferation of complex naming policies would only create confusion for stakeholders and undermine access to high quality biological medicines for patients.
Given recent comments on the FDA’s naming guidance, I don’t think the more “complex naming policy” in the U.S. is going anywhere.
The Generic Pharmaceutical Association (GPhA) has come before Congress in an attempt to increase generic competition in the U.S. As RAPS reports, the organization is particularly interested in making sure the FDA addresses the current backlog in abbreviated New Drug Applications (ANDAs). According to RAPS:
In addition to the ANDA backlog, GPhA is calling on Congress to investigate ‘the abuse by some brand drug companies of FDA programs designed to protect patient safety.’ More specifically, GPhA points to programs, such as the Risk Evaluation and Mitigation Strategies (REMS), which have been misused to prevent the entry of some generics to the market… And although biosimilars don’t fall under the category of generics, GPhA is calling on Congress to further encourage FDA to increase competition for biologics by implementing regulations and policies for approving biosimilars.
While these efforts are directed primarily toward the small molecule generics market, these are worth paying attention to, especially as these challenges will most likely affect or be facing the biosimilar market at some point as well.
AbbVie’s golden child, Humira, might be harder for biosimilar makers to take down than anticipated. According to a recent article in BioPharma-Reporter, Humira is currently protected by more than 70 patents protecting the drug’s formulation, manufacturing, and method of treatment expiring between 2022 and 2034. AbbVie CEO, Richard Gonzalez, said:
Any company seeking to market a biosimilar version of Humira will have to contend with [our] extensive patent estate, which AbbVie intends to enforce vigorously. We believe the litigation process and our intellectual property estate will protect Humira from biosimilar entry until 2022.
AbbVie’s CEO is talking a big game in this article. (I suggest you read the rest of his quotes contained in the hyperlink above.) But I find myself a little less impressed, especially following the news of Genentech’s backing down to Russia’s Biocad over a recent method of use patent (discussed below). It will also be interesting to see how the inter partes review (IPR) process will help biosimilar makers in the face of all these patents.
Russia’s Biocad triumphed over Genentech in a recent patent dispute. The patent for Rituximab is set to expire in 2015 in the U.S., though the patent has already expired in other countries. This opened Genetech up to biosimilar competition (including competition from Biocad) and a sales loss of 90 percent for hemato-oncology treatments in Russia. The Pharma Letter reports that Genentech patented the method of using rituximab, which led to the recent patent dispute. Aleksei Katlov, VP of legal affairs at Biocad, stated:
The patent described that rituximab can be used in combination with other drugs. The instructions to Biocad’s rituximab also indicated that the drug may be used in combination with other drugs. This complete coincidence of descriptions was the reason for the claim.
Interestingly enough, Genentech eliminated the patent rather than going through official proceedings in the Chamber of Patent Disputes. This situation certainly bodes well for biosimilar makers looking to challenge certain patents that might’ve been added as a defensive mechanism onto biologics nearing the end of their patent protection.
The Centers for Medicare and Medicaid Services (CMS) has finalized its proposal for biosimilars under Medicare Part B, choosing to group every biosimilar for a specific reference product together under one Healthcare Common Procedure Coding System (HCPCS). The reference product will remain under a separate code. All biosimilars for a specific reference product would therefore be reimbursed for the same amount of money — a point that does not sit well with generics manufacturers. According to Politico:
CMS disagreed with industry’s argument that the reimbursement proposal would make the biosimilar market less attractive for drug companies. The payment policy should encourage greater competition and improve the quality, price, and access to biologic medicines, CMS said.
The Biosimilars Council, The Biosimilars Forum, and several biosimilar companies have all come out against the final rule. These organizations maintain that not giving each biosimilar its own unique code and payment amount will lead to slower uptake, less biosimilar development, and more confusion in the market. The big issue I'm curious to see now that this has been decided is what happens if (or when) the FDA rules on interchangeability.
According to a Pharma Exec column, the answer is no. To those involved in the October “Biosimilars 2015” Drug Information Association (DIA) conference:
The real drivers in biosimilar uptake will be payers looking to manage rising outlays for increasingly costly biotherapeutics, partly by expanding use of the new comparative products coming to market. Sandoz did not seek interchangeability from FDA due to a higher hurdle to achieving that status, explained Mark McCamish, global head of biopharma & oncology injectables development at Sandoz. But he expects formularies will push lower-priced products, despite efforts by innovator firms to label biosimilars as lower quality because they’re not interchangeable.
I’m curious to see, if this is truly the case, what the likelihood would be of companies in the future striving to garner an interchangeability rating. One official told Pharma Exec that an interchangeable label might increase confidence in the quality and safety of the biosimilar. However, the lack of adverse effects of those taking biosimilars, both in Europe for the past ten years, and in the U.S. as more companies see their products released could also serve this purpose. Given the push for more affordable healthcare in the U.S., and judging from national health plans support of using biosimilars abroad to save costs, I’m with McCamish on this one. I think interchangeability will take a backseat to those attempting to enforce lower healthcare costs.
Even though the deal is far from final, there are already concerns surrounding the prospective merger between Pfizer and Allergan. These concerns are primarily surrounding the combination of their respective drug portfolios — in particular their biosimilar portfolios. Seth Siber, an antitrust lawyer with Wilson Sonsini Goodrich & Rosati told Bloomberg:
The competition issues with biosimilar drugs are very interesting given how new they are to the market. The way a biosimilar drug competes with a branded biologic drug also still isn’t fully understood. This deal tees up a new opportunity for antitrust agencies here and in Europe to think about how to assess competition between these kinds of drugs.
In a recent interview I carried out, one expert identified the Pfizer-Hospira merger as being particularly important for the growth of the biosimilar market in 2016. Pfizer certainly has a goldmine of a portfolio, but I’ve also begun to look at Pfizer as a leader in the biosimilar space because of news like this. As Siber said, Pfizer is a leader in the space because it is encouraging the industry to come up with new ways of assessing the biosimilar market.
According to In-PharmaTechnologist, the European Commission (EC) is planning to introduce waivers to supplementary protection certificates (SPCs) in Europe. SPCs were introduced to extend IP rights for biologics and other medicines in order to make up for the time the manufacturer waited for regulatory approval. The European Generic and Biosimilar Medicines Association (EGA) has expressed its support for this waiver because:
An exemption to SPCs ‘is essential to increase manufacturing and R&D in Europe, create new high skill pharmaceutical jobs, and stimulate economic growth in the EU.’ The EC’s strategy document ‘A Single Market Strategy for Europe — Analysis and Evidence’ said an SPC manufacturing waiver ‘for export purposes to non-EU countries with no SPC protection could allow the EU generics and biosimilars industries both to create thousands of high-tech jobs in the EU and start many new companies.’
Say hello to a bigger biosimilar industry. This could also make the EU an even bigger and more competitive player against the U.S. If more countries see the establishment of new companies, I’m interested to see what rival might arise to challenge the current prominence of South Korea in the market.
RAPS reports that the FDA has received comments on its proposed naming guidance from such groups as the Biosimilars Forum, BIO, and PhRMA. While the FDA originally proposed adding a suffix that is devoid of meaning, industry is now calling for a change to this proposal. RAPS reports:
Industry groups such as the Biosimilars Forum, Biotechnology Industry Organization (BIO), and Pharmaceutical Research and Manufacturers of America (PhRMA) supported FDA's proposal, but called for the agency to use "meaningful" and "distinguishable" suffixes linked to the license holder's name.
However, the Generic Pharmaceutical Association's (GPhA) Biosimilars Council opposed FDA's proposal, claiming that these products "have other names … for distinct recognition; including a brand name, company name, a lot number, and a national drug code (NDC) number that readily distinguish [them] from other products."
These responses don’t surprise me in the slightest. However, I’m particularly interested to see how the FDA goes about navigating the call to work with the WHO to harmonize naming protocol. After all, the FDA’s proposal was similar to that of WHO, which called for a random four-letter suffix. However, I think a good compromise here, if the suffixes are here to stay, would be to continue mirroring WHO, which calls for the proposed suffix to be absent from the nonproprietary name only in pharmacy databases.
Pharma giants Pfizer and Allergan announced they have begun discussions about a proposed merger between the two companies. Not only would this deal lead to a company with a combined market value of $330 billion, but it could have significant impact on the emerging biosimilar market. According to The Wall Street Journal, this move would add several more biosimilars to Pfizer’s pipeline.
Pfizer has been trying to bolster its branded-drug portfolio after recently completing a $16 billion acquisition of Hospira that boosted its off-patent drug business. That could pave the way for a step that Pfizer executives have long been contemplating: breaking up the company into one business selling patent-protecting drugs and the other selling off-patent drugs.
I’ve been curious about how companies producing large brand name drugs, many of which will eventually have biosimilar competition, will handle adding on a competitive biosimilars division. Should this merger take place and Pfizer go through with separating its branded and generics business, I’d be curious to see how many other reference makers with biosimilars in their pipeline follow suit. I’m thinking about Amgen in particular.
In a new article, Pharmatech discusses some of the current challenges impacting biosimilar development in the U.S. Compared to the U.S., which has only seen one biosimilar released after five years following the approval of a regulatory pathway, the EU market has approved 20 biosimilars in the past 10 years, emphasizing the efficacy and safety of biosimilars on the market. Pharmatech says:
Several applications have been under review at FDA for nearly a year, raising questions about whether the U.S. program requires more data than necessary to demonstrate product comparability….A related question is whether CDER and other FDA offices have sufficient resources to provide extensive advisory services for sponsors and to evaluate these products efficiently, following a process that emphasizes analytical comparability of a biosimilar to a reference product.
As the market is still new for the U.S., the hesitation is most likely due to the vast amount of details that still need to be worked out, as well as addressing the amount of lobbying happening that is challenging the legitimacy of biosimilars. But Pharmatech poses some important questions here. As the market becomes more established, the FDA will need to increase the amount of resources it has — and indeed, the agency is reportedly already working on ramping up its biosimilar resources. I read a few weeks ago that the FDA’s biosimilars program is working on upping its spending and manpower to address what will be an increase in biosimilar applications. In particular, the agency has been seeing an increase in work spent on biosimilar product development meetings — a task that has also taken off in the EU recently, as well.
In an attempt to heighten focus on the recently acquired biosimilars in its pipeline, Pfizer returned rights to both a Herceptin and Rituxan biosimilar back to Celltrion. According to FierceBiotech, Pfizer already has a copy of Rituxan in Phase 3 trials, as well as a late-phase version of Herceptin. However, this does not signal the end of Pfizer’s relationship with Celltrion:
Thanks to its Hospira acquisition, the drugmaker inherited a Celltrion-partnered Remicade biosimilar already on sale in Europe, plus early-stage knockoffs of Amgen’s Neupogen and Neulasta.
This move makes sense, seeing as Pfizer wouldn’t be able to keep its hands on both Rituxan biosimilars in the future should one land on the market. However, I’ve also been reading up on biosimilars of Rituximab. I would actually draw your attention to a blog entry (dated 2014) from The Biosimilarz Blog, which discusses the likelihood of a Rituximab biosimilar launching in Europe. There have been Rituximab biosimilars introduced in India, however to this date there are none in Europe, and, as The Biosimilarz Blog points out, there have been a large number of big players terminating their Rituximab biosimilar programs. (In fact, just this week, I caught word that Boehringer Ingelheim pulled the plug on its biosimilar of Rituximab.) There have also been advancements in the standard of care. However, despite the fact Dr. Reddy’s has targeted the EU market as the proper place for its own Rituximab biosimilar, keeping hold on Celltrion’s candidate could’ve given Pfizer another shot at garnering an early spot in the European Rituximab market (should there ever be one).
After reporting disappointing sales figures that demonstrate just how much biosimilars can impact blockbuster sales, Merck has announced a 25 percent price reduction in the U.K. for Remicade. This move is also following the NHS’ guidance arguing that less costly treatments be prescribed over more expensive ones. There’s always a chance, too, that the U.K. has been looking at the impact of discounts in other countries, such as Norway. As FiercePharma reports:
Merck execs have said discounts of the biosimilars have averaged about 45 percent to the price of Remicade. But reports out of Norway said that discounts reached nearly 70 percent…Steinar Madsen, medical director at the Norwegian Medicines Agency, told Bloomberg at the time that doctors felt the price difference was too great to ignore and had been switching their patients from Remicade to the lower-cost biosimilars.
I still remain stunned by how steep a discount for biosimilars we’re seeing in Norway, though, as Fierce says, this discount was the result of a pricing war between two companies, Orion Oyj and Hospira. Let’s just take that as a sign that the more competition on the U.S. market, the more likely we’ll see larger discounts for biosimilars, and perhaps even the reference biologics.
Slate published an article about China’s recent Nobel Prize, which was awarded to Tu Youyou for anti-malarial drug research that led to the development of the drug artemisinin. The article discusses Youyou’s response to the award, which struck some chords with me when thinking about innovation in the biosimilar realm. In Chinese culture, where collectivism is stressed, Youyou told The New York Times in an interview:
We all believed in collectivism. All I wanted was to do good work at my job. Of course, I’d be nothing without my team. Foreign countries like the United States care a lot about which individual should claim credit… This honor belongs to me, my team, and the entire nation.
A few weeks ago, I wrote an article questioning where biosimilars would fall on the innovation scale. I was met with reader feedback, a lot of which was still focused on the fact that biosimilars are copies of existing medicine and, therefore, could not be considered truly innovative. I’m not going to argue with the first point, as biosimilars are indeed a (sort of) copy of an originator molecule. However, judging from the amount of battling between generics and brand makers over the past few months, it’s clear that our country is very engrained in the notion that innovation is an individual accomplishment (or in this case, an individual company’s accomplishment). Creating a biosimilar requires knowledge of the original molecule, which was discovered by another company. However, biosimilar development also requires the ability to work backwards and reverse-engineer a drug that will perform the same way as the reference. The process of manufacturing a biosimilar is a perfect example of collectivism, which, in my opinion, is how innovation works these days. (Open innovation, anyone?)
The Generics and Biosimilars Initiative (GaBi) revealed that biosimilar use increased in Italy from 2009 to 2013. The study specifically examined how various health policies impacted the use of erythropoiesis-stimulating agents (ESAs) in naïve patients. According to GaBi,
Increases in the proportions of biosimilar users were found in Palermo, Treviso, and Tuscany… This may be explained by stringent recommendations for biosimilars use in routine care, such as making it mandatory for ESA prescribers to document the reason why a drug other than a biosimilar is chosen.
An interesting approach here. Always a chance this could backfire; I could see doctors treating this as just another hoop to jump through. But, if taken seriously, it could also be a good way to learn some of the aversions to biosimilars so industry can craft more targeted education approaches.
A press release from Charité Universitätsmedizin Berlin and the University of Massachusetts Medical School announced the publication of an article on the efficacy of rheumatology biosimilars in Nature Reviews Rheumatology. According to the release:
Their review, which covers almost every biological drug available, also addresses the enormous variations currently seen in approval processes across the globe. Their findings suggest that the introduction of biosimilars into clinical practice must go hand-in-hand with the creation of national registers, which allow data on potential side effects to be collated.
The scientists’ desires to see national registers of side effects reminded me of a recent meeting between the FDA and Google. As RAPS discussed in July, the two parties met to discuss a potential partnership, through which the FDA could glean additional information about adverse drug effects using search engine logs and Google technologies. Nothing is official here yet — at least as far as I’ve heard. But the research by the two universities got me thinking about the usefulness of this partnership for biosimilars. Seeing as there are a number of concerns about switching patients from the biologics to a biosimilar, a partnership like this could be beneficial for the industry to gain insights on those taking both the biologics and the biosimilars. It could maybe also serve as a good tool to learn the areas of each treatment where there needs to be more patient education about biosimilars.
At the CPhI Worldwide event in Madrid, Christoph Bieri, a managing partner at M&A advisory firm Kurmann Partners, discussed the escalating occurrences and transaction sizes of pharma industry mergers and acquisitions. Following the predicted burst of the biotech bubble, Bieri expects pharma companies to continue restructuring in accordance with four strategic archetypes, especially as R&D costs increase for mid-size pharma companies. According to In-Pharma Technologist, larger generics and biosimilar makers will use M&A to gain market access and production capacity.
I was wondering if we were going to see the same trend of consolidation we’ve been seeing in the generics industry as of late (Teva/Allergan, Mylan/Perrigo). If Bieri is right, the Big Generic age will translate to Big Biosimilar in the future as well.
It might seem that the biosimilar space is still small, but according to BioPharma-Reporter, the number of biosimilar developers is on the rise. There are currently around 245 biopharma companies at work developing biosimilars, many of which have entered the space because of decreasing development costs. Richard Dicicco, chairman of Harvest Moon, states:
If you look at the analytical stage, which is the most important part of a biosimilar, it costs $7 to $15 million and takes four years, and you don’t do anything until you have the data on the originator molecule. In the future, maybe past 2020, there won’t be a need for confirmatory Phase 3 studies which the industry is scaring you on. Don’t be afraid of $150 million because it’s not true — I could develop three molecules for that.
Definitely a sign of good things to come from this space — as well as increasing company confidence in the market prospects for biosimilars.
The Federal Circuit turned away rebuttals from the Amgen vs. Sandoz fight over the recently-ruled-upon patent dance. However, as Law360 discusses, the Circuit’s decision not to listen to the continuing arguments has left four questions unanswered, including:
Why did the Federal Circuit deny a rehearing?
Does Supreme Court review loom?
Can the 180-day notice requirement be escaped?
What does the patent dance require?
The question about escaping the 180-day notice should especially be of interest. Paul Calvo of Sterne Kessler & Fox PLLC asks:
If you do the patent dance, maybe you don’t even need to provide notice of commercial marketing. That’s just hanging out there in the wind. If the parties actually dance, then is the 180-day notice actually mandatory under the statute?
The answer to this question would prove quite useful, I’m sure, for a number of biosimilar makers in BPCIA fights, including Amgen and Hospira, Amgen and Apotex, and Janssen and Celltrion, Law360 outlines. This definitely won’t be the last we hear of this question.
A couple of weeks ago, California’s governor signed Senate Bill 671, which gives permission to pharmacists to dole out interchangeable biosimilars for biologics. This bill will be applicable to any pharmacist filling a biologics prescription that does not prohibit substitution. In an article for JDSupra Business Advisor, Joanne Hawana and Sarah Beth Smith of Mintz-Levin-Health Law & Policy Matters explained the recent bill, stating:
After dispensing any biological product, the law requires the pharmacist or her designee to communicate to the prescriber within five days the name and manufacturer of the biological product dispensed, and the communication should be given via an electronic records system or other means if an electronic records system is unavailable. … Patients must also be notified of the substitution, but the law does not discuss when, how, or who must communicate this information to them….California’s new law does not mandate specific recordkeeping requirements following the dispensing of an interchangeable biosimilar.
The last part of that ruling raises a few questions for me. Given the fact that biosimilars have been given suffixes to ensure safety, I think it will be interesting to see if there are any challenges to this, and if other states will follow in California’s footsteps. Reference makers will be less than pleased; but this moves gives me some hope that there is already some trust in biosimilars, even though our market has yet to become populated.
According to BioPharma-Reporter, Celltrion’s Remsima biosimilar is expected to overtake Johnson & Johnson’s reference biologic Remicade. At the CPhl Worldwide Pre-connect Congress in Madrid, Steinar Madsen, medical director of the Norwegian Medicines Agency, discussed the current findings of a study launched in 2013 examining the effects of switching patients from Remicade to Remsima. This study recently was extended due to the fact that, as Madsen says:
‘[Remsima is] so cheap, it is difficult to find patients still using Remicade. There will be an almost total wipe-out of the originator drug by 2016’ thanks to high discounts, switching occurring at the discretion of hospitals/physicians, and increasing management involvement in biosimilar advocacy.
But I also found what Madsen said about the topic of interchangeability to be well articulated:
The big myth here is that there is a gold standard, but in fact, all biological products are biosimilars. Due to the nature of these products, every manufactured batch is different.
Amen to that.
After the recent Trans-Pacific Partnership (TPP) agreements, there have continued to be discussions about intellectual protection of medications abroad, especially in least-developed countries (LDC). The World Trade Organization (WTO) held a meeting today to determine whether the poorest countries should be exempt indefinitely from abiding by pharmaceutical patent rules. As RAPS reports:
The exemption allows local manufacturers and other international programs to supply necessary drugs…in affected countries without having to deal with patent infringement lawsuits. As the current exemption on medicines is set to expire at the end of this year, Bangladesh, on behalf of the 48 LDCs, requested that the WTO change the exemption to last as long as countries remain LDCs.
After the recent TPP negotiations, I imagine this is going to be a sore spot, especially for the U.S. which had some aversions to the final agreements over biologics data exclusivity. Not sure how realistic is it to expect the U.S. in particular to accept indefinite exemption from IP, but it sounds as though PhRMA is in support of some kind of extension of the LDC waivers. So far, this proposal has support from the European Commission, the WHO, the United Nations Development Program, Norway, and several Democrats including U.S. presidential candidate Bernie Sanders.
Michel Mikhail, a biosimilar regulatory consultant, discusses the recent FDA naming guidance and the impact he expects it will have on the upcoming guidance on interchangeability in BioPharma-Reporter. He states:
[By assigning a random four-letter suffix to each biosimilar name] the FDA has put itself in a catch-22 situation. The proposal to have an International Nonproprietary Name (INN) with an added four-letter rule has left the FDA trapped. When interchangeability guidelines come along, there shouldn’t be any need for this four-letter distinguisher.
Mikhail makes a good point here, but the louder voices in the industry are still going to push for the differentiating suffixes for safety purposes. So even if it’s a catch-22 for the FDA, a four-letter suffix isn’t really going to make a whole lot of difference should a biosimilar be deemed interchangeable.
MedPage Today published an article making the argument that Rituximab, often used to treat leukemia and lymphomas, should not be ruled out as a treatment for multiple sclerosis (MS). Recent clinical research efforts have illuminated the drug’s potential to be superior to the newer anti-CD20 biologic ocrelizumab.
Researchers involved in the ocrelizumab trials say they think the newer agent will eventually prove to be superior — it is a humanized monoclonal antibody, whereas rituximab is chimeric, and infusion reactions and anti-drug antibody responses may be lessened with ocrelizumab (although this remains to be proven.) But clinical reports on rituximab in patients with both relapsing-remitting and progressive forms of MS indicate that the drug is both highly effective and well-tolerated.
This certainly promises to bode well for biosimilar makers should this indication ever be added to Rituximab’s label, especially seeing the rate of MS drug price inflation.
Forbes columnist Grace-Marie Turner discusses the latest Medicare payment rule that would lump all biosimilar drugs for the reference product together, in turn ensuring they are the same price. According to Turner:
This rule could have huge implications on whether this fledgling industry thrives. It is also a perfect example of a government-centric policy: Before this new market of biosimilars has even become well-established, CMS wants to slap it with price controls that will discourage new entrants and the vibrant competition that works to increase quality, supply, innovation, and lower costs based upon greater competition.
Turner provides an interesting point of view here, one I hadn’t thought about at much length. It sounds a lot like the battle over the recently proposed FDA naming guidance. In this particular instance, the House is seeking unique payment codes for each biosimilar. (Sound familiar?) Considering however, that the FDA took the road of issuing special four-digit suffixes for each biosimilar, just to ensure safety, I can’t imagine this system of filing various biosimilars under one code will make it through.
RAPS reports that the European Medicines Agency (EMA) has found that, in the first half of 2015, 77 percent of marketing authorization applications (MAA) for biosimilars and NMEs sought out scientific advice from the EMA earlier in the drug development process.
“This demonstrates that EMA’s efforts to encourage medicines developers to seek interaction and dialogue with the agency are paying off,” EMA said. In addition, the number of requests for scientific advice and protocol assistance rose by 6 percent compared to the same period last year.
Glad to hear this is the case for biosimilars. This trend can only benefit the market.
NHS Defends Against Lack Of Guidance Accusation (10.6.15)
According to BioPharma-Reporter, Napp Pharmaceuticals went up in arms about the amount of time it has taken the U.K.’s National Health Service (NHS) to adopt Remicade biosimilars. Napp argued that this lag has to do with a lack of NHS guidelines. However, this week, the NHS fought back. In a statement, Chief Pharmaceutical Officer of the NHS Keith Ridge wrote that the guidelines recently put forth by the NHS:
Provides key clinical and non-clinical stakeholders with accessible information on how to support the appropriate use of all biological medicines, including biosimilar medicines for the benefit of NHS patients. As the range of biosimilar medicines increases, it is important that the NHS plans for their timely, appropriate, and cost-effective introduction. Therefore, all staff in the NHS, from senior managers to commissioners, through to front line health professionals need to understand more about biosimilars.
I do find it a little bit odd, though, that from my research at least, Norway doesn’t have any written specifications in place about interchangeability, which could influence the uptake of biosimilars. (Sounds like a lack of guidance to me…) Norway was also the first country to undertake a switching trial to determine the effect of switching patients from the biologic to the biosimilar. Seems to me like something that could affect the trust and uptake of biosimilars.
The high-profile Trans-Pacific Partnership (TPP) negotiations were resolved early this week, leaving several different parties — especially the pharmaceutical industry — feeling disgruntled. According to RAPS:
The deal…would either provide eight years of exclusivity to biologic drugs, or provide five years of exclusivity, plus up to three more years under a regulatory framework for the 12 countries in the trade bloc, which includes the U.S., Australia, New Zealand, Canada, Japan, and Malaysia...Trade representatives from the U.S. and Japan favored a longer period of protection — up to 12 years — while others, such as Australia, expressed fears that delaying the entry of biosimilars for that long would raise costs.
BIO and PhRMA are far from pleased with this arrangement, citing concerns about the impact this decision will have on innovation and global drug development for patients. Nonprofits are upset that protection was set for eight years rather than five, encouraging monopolies and holding back the delivery of affordable medicines to developing countries. To say the entire pharma industry is upset by the agreement, however, strikes me as inaccurate, considering this agreement has shortened the amount of time biosimilar makers have to wait to release their biosimilars. In fact, the Biosimilars Council released a statement supporting the decision. It does occur to me, however, that these new regulations can also hurt biosimilar makers and certain developing countries — especially those that had exclusivity laws for five years or less (or no exclusivity for biologics in the first place).
Earlier this year, there was a great amount of protesting over the U.K.’s National Institute for Health and Care Excellence’s (NICE) decision to no longer pay for Roche’s Kadcyla drug. The Pharma Letter writes that a pressure group is now calling for a compulsory license for Kadcyla to permit biosimilar makers to make a cost-effective version of the drug that would be covered by the National Health Services (NHS). Jacintha Sivarajah of the Association of the British Pharmaceutical Industry (ABPI) tells The Pharma Letter:
The U.K. Intellectual Property Office could, in theory, grant a compulsory license for a patented product in the U.K. This could be because someone applies for a license, or because the government decides that its needs are greater than the license holder’s… However, compulsory licenses are very rarely applied for or granted in the U.K. except in exceptional and extreme cases, such as a major pandemic, the ABPI would not support compulsory licenses as they undermine the intellectual property system and threaten innovation.
Doesn’t sound promising for those companies chomping at the bit to make Kadcyla biosimilars.
According to Generics and Biosimilars Initiative (GaBI), The Netherlands has launched the NOR-SWITCH study to determine the effect switching patients from the biologic Remicade to an infliximab biosimilar will have on overall treatment response. GaBI reports:
The study will enroll 200 rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis patients who are currently treated with Remicade. The patients will be informed about the option to switch to infliximab biosimilar. Both patients who switch treatment to biosimilar infliximab (switch group) and patients who do not switch treatment (control group) will be asked to participate in this study.
Norway was the first country to do this, and I know the U.S. is attempting to put together some guidance on how to go about carrying out these trials. I’m excited to see some progress being made with this process, considering this is one of the key concerns standing in the way of many countries’ rulings on interchangeability.
Second Sandoz Biosimilar BLA Accepted By FDA (10.2.15)
The FDA has accepted for review a BLA for Sandoz’s biosimilar for Amgen’s Enbrel. The company’s goal is to have the biosimilar approved for all the same indications as Enbrel. Included in the BLA were data from two pivotal clinical studies, one carried out in healthy volunteers and another in patients with chronic plaque-type psoriasis. Mark McCamish, the head of global biopharmaceutical and oncology injectables development at Sandoz says:
Anti-TNFs will continue to play a leading role in immunology treatment and the acceptance of our regulatory submission by the FDA today is a significant step towards increasing patient access to these life-changing medicines. We believe we are the first company to receive FDA file acceptance of a biosimilar version of etanercept.
So far, the biggest contenders for Enbrel biosimilars are Merck & Samsung Bioepis, which saw their own biosimilar win approval in South Korea. Samsung Bioepis and Biogen Idec are also well on their way to gaining European approval for their Enbrel biosimilar. While I think a lot of companies are particularly hesitant to pursue biosimilar approval in the U.S. because of market and regulatory uncertainty, we should be giving props to Sandoz. They seem particularly fearless about making the U.S. market their own early on.
FiercePharmaMarketing reported this week that Novartis and DC Comics have teamed up and released a new graphic novel to educate teens about the rare disease tuberous sclerosis complex (TSC). As Fierce reports:
The Swiss Pharma giant designed the comic to “help patients understand the challenges” of the rare genetic disease — “from seizures, skin lesions, and tumors in vital organs to multiple doctors’ appointments — and empower them to talk to others about it.”
There’s a great need to educate patients on what biosimilars are and how they work. While a graphic novel might not necessarily be the best for all audiences, it could be a good way to educate parents and younger patients that might be receiving biosimilar treatments.
Novartis is also looking at this as a method to promote its cancer blockbuster, Afinitor, as it is about to face competition from Bristol-Myers Squibb’s Opdivo and from Pfizer’s Ibrance. Just as the graphic novel could be used to educate patients about the disease itself and the ways to go about treating/handling the symptoms, this could also be a way for drugmakers to promote their reference biologics in the face of biosimilar competition.
Celgene’s efforts to sanction Kyle Bass for his use of the inter-partes review (IPR) process against pharmaceutical patents were overturned yesterday. Reuters reports that the Patent Trial and Appeal Board (PTAB) did not find anything remiss in Kyle Bass’s actions, opening the door for other hedge funds to target pharmaceutical patents using IPRs. According to the PTAB:
Profit is at the heart of nearly every patent. As such, an economic motive for challenging a patent claim does not itself raise abuse of process issues.
I find the PTAB’s reasoning here to be sound and well-put. Even though this might seem like a loss for the pharmaceutical industry, it won’t be a loss for all parties within pharma. Biosimilar makers have been using the IPR process to challenge biologics patents, much to reference makers’ chagrin. BIO and PhRMA have even gone so far as to argue that pharma patents be exempt from the IPR process — and, at the very least, that generics/biosimilar makers be limited to the Hatch-Waxman Act for challenging originator drugs. If the PTAB isn’t overturning Bass’s efforts though, I have a hard time believing it’s going to ban biosimilar makers from this process.
Lilly’s Lantus Biosimilar U.S. Entry Delayed (9.29.15)
PMLive reports that Sanofi and Eli Lilly have reached an agreement that will push the entry of Lilly’s Lantus biosimilar onto the U.S. market back to December 2016. According to PMLive:
Under the terms of the agreement, Lilly has agreed to pay royalties to Sanofi in exchange for a patent license from Sanofi, and has agreed to hold off on launching its own pen-based insulin glargine product Basaglar — partnered with Boehringer Ingelheim — until December 15, 2016…Delaying direct competition in the U.S. will avoid a dramatic fall-off in Lantus sales for another 12 months.
This is certainly good news for Sanofi, and it has ended what seemed like endless patent litigation between the two parties. But this also means that other companies could work out similar deals in the future, which only means more delays in the growth of the U.S. market.
AbbVie announced it will no longer be pursuing an acquisition of a rheumatoid arthritis treatment being developed by Galapagos. This news came after AbbVie’s own experimental drug ABT-494 improved rheumatoid arthritis symptoms in mid-stage studies. Analysts are claiming this decision to overlook Galapagos’ candidate could end up being good for the company. Reuters reports:
If AbbVie’s drug ABT-494 succeeds in late-stage studies and is approved, analysts said that would help spare the suburban Chicago company about $1 billion in royalties it would have had to pay Galapagos for its pill, called filgotinib…Tests showed filgotinib to be more effective than AbbVie’s drug in targeting enzymes that cause inflammation in rheumatoid arthritis, Galapagos said.
Avoiding a $1 billion in royalties I’m sure is an appealing prospect for a company that is quaking in its boots over the patent expiration of its lucrative Humira. It’s good, too, to hear that the company is working on bolstering its pipeline in the age of dwindling pipelines and excessive acquisitions/M&A. Though, it is a bit concerning that the company is overlooking what might be a more effective treatment. If Galapagos is being truthful, AbbVie’s candidate could just end up being another me-too drug — and a me-too drug isn’t going to be capable of replacing Humira.
Firstword Pharma published a ViewPoints column discussing Amgen’s biosimilar strategy. According to Firstword Pharma’s own Duncan Emerton:
I agree that taking the ‘if you can’t be ‘em, join ‘em’ approach to biosimilars could reap rewards for Amgen in the future.
But most interesting to me was the question the ViewPoints author Simon King posed at the end:
Having moved aggressively to thwart the launch of biosimilar competitors to its own brands, what rules will Amgen play by when the tables are turned?
It’s a fitting question to ask, considering the amount of protesting Amgen has been doing to protect its reference products from emerging biosimilars. I think pharma companies making both reference and biosimilar products are facing a future in which they will need to come up with ways to address what is, essentially, a split identity. Ultimately, a company is going to need to build a biologics pipeline that pushes the envelope in treating unmet health needs and asserts the value of biologics for society in the same way biosimilars boast the value of cost-effective healthcare. For Amgen, and for any reference maker exploring biosimilars as well, the battle will always be about protecting its biologics revenue and fighting tooth-and-nail to garner revenue from other companies’ expiring blockbuster patents.
Last week, the NHS released a guidance recommending that “automatic substitution” of biosimilars at pharmacies be banned, BioPharma-Reporter stated. Doctors are still able to specify that the patient is allowed to receive a biosimilar, and, pending their permission, switching may occur as long as there is some monitoring system in place to ensure the patient’s safety. According to BioPharma-Reporter:
The rule will change the way doctors write their prescriptions. British medics are taught to prescribe using a medicine’s generic name or international non-proprietary name. But in the U.K., biosimilars use the same INN as the reference product. To prevent accidental substitution, doctors in England will have to prescribe biologics — whether an originator or a biosimilar — using their brand name.
This is in line with what the Medicines and Healthcare products Regulatory Agency has called for (MHRA) in terms of substitution, but this recommendation overall could be a blow to biosimilar makers in the U.K.
The NHS has released a new document titled “What is a biosimilar medicine?” The publication was put forth by the Medicines and Healthcare product Regulatory Agency (MHRA), National Health Service (NHS) England, the National Institute of Health and Care Excellence (NICE) and other pharma trade organizations, The Pharma Letter reported this week. The Chief Pharmaceutical Officer of NHS England, Keith Ridge, stated:
As the range of biosimilar medicines increases, it is important that the NHS plans for their timely, appropriate, and cost-effective introduction. Therefore, all staff in the NHS, from senior managers to commissioners, through to front line health professionals need to understand more about biosimilars.
Here’s hoping this publication will play the role of a much-needed educational resource for the industry.
2015 FDA Biosimilar Spending, Workload On The Rise (9.24.15)
A new report from Eastern Research Group (ERG) this week has revealed the FDA is only finally starting to increase spending and manpower on its biosimilars review program. The goal of the ERG report is to determine the workload and costs of reviewing biosimilar applications. According to RAPS:
The largest category of work for FDA has been in performing Investigational New Drug (IND) and pre-IND work, including biosimilars product development (BPD) meetings (55.8 full time employees, or FTEs.) Policy work (23 FTEs) and then science and research work (21.0 FTEs) were the second and third largest categories of work…Interestingly, the report also notes the vast majority of biosimilars work performed by FDA through the 31 of March has been performed by Center for Drug Evaluation and Research (CDER).
Obviously, we should keep expecting this to go up as the year goes by — according to RAPS, of the five 351(k) biosimilar BLAs the FDA has received between 2013 and 2015, five of them landed on the FDA’s desk this year.
Australia Pharma Seeking Joint Ventures: Could This Impact Biosimilars? (9.24.15)
According to The Pharma Letter, a number of Australian pharma companies are looking to enter into joint-ventures over the course of the next two years. This information, captured in the PriceWaterHouseCoopers (PWC) survey of the Australian medicines industry, reveals that:
Two-thirds of companies said they expect growth in the Australian market. Growth is expected to come largely through expansion in new therapeutic areas, increases in sales and marketing capacities, the introduction of new products in portfolio pipelines, and New Chemical Entities (NCEs).
I’ve been reading quite a bit about Australia as of late and the nation’s biosimilar market. I wonder if these joint-ventures will have anything to do with biosimilar collaborations, especially seeing as Australia is looking to bolster its biosimilar market to draw more Big Pharma attention.
Amgen-Allergan Lung Cancer Biosimilar Shows Promise (9.23.2015)
Amgen and Allergan announced that their biosimilar candidate to Roche’s Avastin was successful in a late-stage lung cancer study. According to Reuters:
If approved, the Amgen-Allergan drug, ABP 215, would be Amgen’s first biosimilar on the market. The company has eight others in development.
Exciting news! After all of Amgen’s attempts to protect itself from biosimilar competition, it’s looking like it could be one of the first players out the gate when Avastin’s patents expire in 2019.
Infliximab Biosimilars Making Headway In Europe (9.23.15)
According to Reuters, biosimilars have taken root in Europe, despite the lack of clarity over interchangeability within many of the individual nations. Overall, the article focuses on the discounts for the infliximab (Remicade) biosimilars being offered in various nations overseas. Alan Sheppard, global head of generics at IMS Health, told Reuters:
I don’t think anybody thought infliximab would be discounted to such an extent and that switching would come into some markets quiet so aggressively.
But I was also struck by this information:
IMS data shows that Poland...leads the field with biosimilars accounting for 80 percent of infliximab use. Norway follows with a two-thirds biosimilar share, while Finland and Hungary both have around one third. In the big European markets the penetration rates are much less, at around 10 percent in Germany and Spain, with British use even lower.
So what do Poland and Norway have that the other countries don’t? No written regulations for or against interchangeability (Poland) and steep discounts. (In Norway, infliximab goes for 69 percent less than Merck’s reference). Spain and Germany forbid substitution, and the U.K. pushes its doctors to prescribe using the brand name only. It’s not rocket science — the biosimilar market will grow if interchangeability isn’t strictly prohibited and biosimilars are available at a larger discount than reference products.
Clinton To Go After Biologics Exclusivity (9.22.15)
This week, Hillary Clinton announced plans to address high drug prices in the pharmaceutical industry — an announcement that led to a quick drop in drug company stock prices. According to MSNBC, one way she plans to do this is by lowering the exclusivity period of reference biologics. MSNBC says:
Clinton would expand the availability of generics by boosting the FDA’s capacity to approve the drugs, and she’d decrease the intellectual property protections for expensive biologic drugs so generics could be produced faster.
The Street says she plans to lower the period from 12 years to seven, which was one of the options being batted around during the Trans-Pacific Partnership (TPP) agreement. Though, after the failure to come to an agreement about the biologics exclusivity period, I don’t think she’s going to win this particular fight. Some politicians and Big Pharma’s interests are just too tightly intertwined for there to be a significantly meaningful shortening of exclusivity periods.
FDA: “Bulletproof” Biosimilar Science Key To Successful Market (9.18.15)
The FDA’s Janet Woodcock spoke before the Senate Subcommittee on Primary Health and Retirement Security this week, defending the agency’s slow progress in releasing guidances on interchangeability. In order to release these guidances, the agency needs to ensure the scientific framework is “bulletproof,” said Woodcock. RAPS describes,
The most heated exchanges came between Woodcock and Sen. Elizabeth Warren, who seemed particularly peeved about the delay in FDA's release of a number of guidance documents, particularly on interchangeability and labeling. ‘We have to get the science right. We can't have problems with the first biosimilars out of the block,’ Woodcock told Warren. Woodcock added that the remaining guidance documents that have yet to be issued are mostly tied to policy, rather than scientific issues.
Woodcock is right — a poorly performing biosimilar on the market this early would certainly cause a lot of damage. But I did find it rather interesting that the next guidance we should expect to see is the one titled “Statistical Approaches to Evaluation of Analytical Similarity Data to Support a Demonstration of Similarity.” This guidance, according to Woodcock, is the third most important guidance behind labeling and interchangeability. It’s strange to me they’d choose to focus on the third most important guidance, rather than the second most important guidance on interchangeability. Seems to me this decision is validating Warren’s frustration at the slow release of the interchangeability guidance, rather than supporting Woodcock’s argument.
Biosimilar Discounts Ride On FDA Interchangeability Decisions (9.18.15)
According to a Berkeley health policy expert, interchangeability is going to the key to long-lasting price competition in the U.S. biosimilars market, BioPharma-Reporter states.
Patients treated with interchangeable products are not captive of a given brand. As a consequence, and according to state laws that govern substitution, there could be a long-lasting competition for chronic treatments.
It’s interesting to see the differences in pricing according to the various countries. BioPharma-Reporter states that:
Pfizer’s unit Hospira was contracted by France’s Assistance Publique to supply its version of Merck & Co’s Remicade (infliximab) at a 45 percent discount to the originator. However, in Norway, the same drug sells for 69 percent less than the Merck original.
It makes sense that, because Sandoz’s filgrastim hit the market first and is currently devoid of biosimilar competition that it would only be priced at a 15 percent discount in the U.S. But the differences between the U.S. price discount and Norway’s is staggering. I’m going to take a wild guess and say we won’t ever see prices for a biosimilar at such a discounted rate here in the U.S. But here’s hoping more competition will get us closer to the discounts in France.
Roche: “It’s Good We Have Biosimilars” (9.16.15)
Roche’s CEO Severin Schwan told The Wall Street Journal that biologic exclusivity periods are an ideal and successful system for societies:
If you don’t have biosimilars…the whole model would collapse because societies would not give you a premium [for innovative drugs] anymore…it’s good we have biosimilars and that they give oxygen to payers.
Amidst the ongoing lawsuits between biosimilar and reference makers, I found this to be a refreshing perspective coming from a brand maker.
J&J CEO: Biosimilars Present Different Threat Than Generics (9.15.15)
Once again, Johnson & Johnson’s CEO, Alex Gorsky, has come out saying he firmly believes the U.S. biosimilar market will impact reference drugmakers in a different, less severe way than that of the generics market. BioPharma-Reporter cites Gorsky at last week’s Wells Fargo 10th Annual Healthcare Conference:
If it weren’t for generic drugs, if it weren’t for biosimilars to a certain degree, there would be no way that we could sustain an innovation-based healthcare system, because you wouldn’t have any pressure relief in the system… We know from our own experience with Procrit (epoetin alfa) a number of years ago, that a very minute change in a component of one of the packaging material can end up having an impact on protein itself and on the way that it manifests itself clinically in terms of immunogenicity and side effects. And so to think that a biosimilar is going to have the exact same clinical effectiveness, the same side effect, just isn’t the case.
I don’t think Gorsky is too far off base here. For those patients taking reference treatments and seeing benefits, change to a biosimilar would probably be unwelcome. But there still has yet to be a decision on interchangeability, and this decision could shake things up a bit.
GPhA Protests FDA Guidance On Generics’ Physical Attributes Requirements (9.15.15)
The GPhA has begun questioning the legality of the recent FDA guidance stating that generic drugs should be as close in size, shape, weight, etc., to that of the originator drug as possible. As RAPS reports, in its letter to the FDA, the GPhA states:
Where Congress permitted generic drugs to vary from the RLD, e.g., in manufacturing methods and in formulation, Congress provided for FDA to ensure that the generic drugs are safe and efficacious. Hatch Waxman specifically states that FDA may not require more than what is required to satisfy those statutory requirements. Hence there is no provision in Hatch Waxman allowing FDA to deny the approval of an ANDA [abbreviated new drug application] based on differences in physical attributes between a generic product and the RLD. The premise of the guidance, that generic drugs must mimic the reference listed drug in size and shape, has no basis in law.
At the present moment, manufacturers are relying on injected formulations for biologics since biologics have been too complex for pill form. However, I am aware of some work being done, to find ways to make a biologic into pill form—for instance at MIT with its “needle pill”. It might take a while, but I expect as technology continues advancing, we’ll see the advent of biologics in pill form. If that ever becomes the case, it will be interesting to see if the FDA puts forth a guidance specifying similar physical attributes for biosimilars. Given all the concerns over the fact that a biosimilar is only just “similar” to the reference product, I bet this is a conflict that arises as the FDA attempts to eliminate other factors that might affect the performance of the drug in the body.
AbbVie’s Humira Wins Ninth Indication In U.S. (9.14.15)
AbbVie won yet another nod from the FDA this week, making it the first approved drug to treat hidradenitis suppurativa, an inflammatory skin disease. As PMLive reports:
The approval is based on data from two Phase 3 trials — Pioneer I and Pioneer II — which included 633 people with moderate to severe HS. Both studies showed that more patients given Humira (adalimumab) had reductions in total number of abscesses and inflammatory nodules than patients who received placebo.
Well, Humira has become even more of a golden child. We better hope that extrapolation is permitted in the U.S. in the near future because AbbVie just secured a new niche for Humira in the market. It’s going to take biosimilar makers a long time and a lot of paperwork (and money and trials) to get their versions approved for everything Humira can do — and there are quite a few makers out there tinkering with adalimumab. It actually makes me wonder if AbbVie should really be that worried in the first place about competition.
EC Supports Disregard Of Drug IP In LDCs (9.11.15)
According to RAPS, the European Commission (EC) has come out in support of a proposal that would enable least-developed countries (LDCs) to import, manufacture, and supply generic drugs regardless of existing patent protection. European Commissioner for Trade Cecilia Malmstrom said:
The poorest countries of the world need effective access to medicines. Although patents stimulate innovation in developed and emerging economies, intellectual property rules should be a non-issue when the world's poorest are in need of treatment. This exemption will give the least developed countries the necessary legal certainty to procure or to produce generic medicines.
After all the back and forth and indecision over biologics exclusivity periods during the Trans-Pacific Partnership negotiations, this news is a good omen for biosimilar makers.
Merck, Samsung Win South Korean Nod For Biosimilar (9.8.15)
Merck and Samsung Bioepis, partners since 2013, won an approval from South Korea’s Ministry of Food and Drug Safety for their biosimilar of Amgen’s Enbrel. FierceBiotech reports:
Korea's Ministry of Food and Drug Safety signed off on the injection, to be marketed as Brenzys, to treat rheumatoid arthritis, psoriatic arthritis, spondyloarthritis and psoriasis in adults. The biosimilar, developed as SB4, proved itself equivalent to Amgen's cash cow in a 596-patient study disclosed this year, reducing symptoms of rheumatoid arthritis on pace with its reference product.
Samsung Bioepis is on my list of players to watch. They’re off to a good start — Biogen Idec and Samsung just saw success bringing their biosimilar of Remicade into the EU.
Roche Responds (Poorly) To UK’s Cancer Drug Decision (9.8.15)
Bloomberg reports that Roche’s CEO Severin Schwan expressed his displeasure over the U.K.’s decision to cease funding Roche’s breast, cervical, and colorectal cancer drug Avastin. Roche’s drug is just one of 16 medicines used in 23 different cancer treatments that the Cancer Drugs Fund in England has axed because of concerns that the drugs cost too much and don’t provide enough benefit to the patient. Bloomberg explains the consequences of this decision:
The decision may mean that Roche will not able to do clinical trials in the U.K. in the future because it will not be able to test new drugs against Avastin, which is the current standard of care for some cancers, according to Schwan.
Not only could this decision be problematic for patients, I’m concerned about what this will mean for biosimilar development. If we think about this from an interchangeability standpoint, how will those testing biosimilars be able to establish comparability?
Are IPRs Really Going To Help Biosimilars Fight Brand Patents? (9.4.15)
The past few weeks, the industry has been setting its sights on the latest Kyle Bass Inter Partes Review (IPR) challenges of blockbuster drugs’ and biologics’ patents. This new process, often referred to as the IP death squad, has led many in the pharma industry to become concerned about the impact of the IPR on drug patents. However, as FiercePharma discusses, Bernstein analyst Ronny Gal claims that:
‘[The IPR challenge] is not much of an IP death squad’… While the comparatively speedy nature of IPR review has some drugmakers — and their investors — worried, the stats so far ‘suggest 15 percent of patents challenged via IPR are invalidated’ and that’s ‘reasonably similar to patent challenges via the court system.’
I wrote not too long ago on this thread that biosimilar makers have jumped onto the IPR wagon in an attempt to lower the number of patents standing in the way of competition. So far, IPRs have been more helpful for challenges in the tech space, but it seems that’s starting to change. I think these IPR challenges are certainly important to keep eyes on, and the frequency of challenges on pharma patents will likely continue to increase. But these challenges very rarely affect the key patents, nor do they eliminate a large enough number of them to harm a brand-name drug’s market exclusivity.
Biosimilar Manufacturers Call On FDA For Interchangeability (9.4.15)
According to BioPharma-Reporter, Zarxio, which just debuted in the U.S. market this week at a 15 percent discount, has not yet been deemed interchangeable with Neupogen. Biosimilar developers are anxious to see the FDA make some decisions on interchangeablility. According to a quote cited from Health Affairs:
Initially, modestly discounted biosimilars deemed noninterchangeable with the original products will compete to become the initial treatment of choice in new patients. Subsequently, a second market may be anticipated for those products able to meet the FDA’s higher standard for ‘interchangeability.’ In that market, discounts may be more dramatic.
So establishing a biosimilar as interchangeable could be the way to achieve the 40 and 50 percent reductions that insurers are hoping for.
Pharma Upset With France Over Avastin Decision (9.3.15)
As FiercePharma reported, the French government has approved of the off-label use of Genentech’s Avastin for wet age-related macular degeneration (AMD). However, this has led a European industry organization to launch a complaint with the European Commission because of fears that off-label use could harm patients asAvastin has not been through the appropriate EU approval process, nor has it been tested in clinical trials, Roche argued. According to FiercePharma:
Last year, the government named Avastin as a substitute for its pricier counterpart, Novartis and Roche's eye drug Lucentis. Putting Avastin on the official reimbursement list for AMD "will achieve significant savings," France's minister of health Marisol Touraine said in a statement, an attractive prospect given the rising costs of prescription drugs in Europe. Lucentis costs 30 times more than Avastin in France, lawmakers pointed out last year, and switching patients over to the cheaper therapy could save the country €200 million ($273 million) a year.
Avastin has patent protection in the EU until 2022…
Novartis Establishes Zarxio Pricing (9.3.15)
Today, Sandoz’s biosimilar for Amgen’s Neupogen hit the U.S. market. According to Reuters:
Novartis said the U.S. wholesale list price for a 300 microgram syringe of Zarxio was $275.66, with the 480 mcg version costing $438.98. Neupogen costs $324.30 and $516.45 for the same syringe formulations, according to Amgen. The 15 percent discount is the same price gap set when Zarxio was launched in Europe in 2009, although the discount in Europe has since widened to an average of around 20 to 30 percent.
We’re not seeing a huge amount of price differentiation here, though at the end of the day, biosimilars are biologics. Reuters says insurers would like to see this 15 percent grow to 40 or 50 percent. That seems a little optimistic to me.
Novartis Cleared To Sell Zarxio (9.2.15)
Reuters reports that a U.S. appeals court has upheld the July ruling of the U.S. Court of Appeals for the Federal Circuit that Sandoz can begin selling its Zarxio biosimilar on July 3, 2015. Reference brand maker Amgen has challenged the release of the biosimilar lawsuit launched last October claiming Sandoz had infringed on one of Neupogen’s patents. The appeals court provided no reasons for why it chose to reject Amgen’s latest bid demanding that the biosimilar remain off the market.
I don’t think anyone will be surprised by this. Biosimilars have been a long time coming; I dare say one more challenge from a disgruntled reference maker is going to keep the market from officially emerging in the U.S.
Pfizer’s Infliximab Seeking Big Name Acquirer (9.1.15)
There aren’t any suitors lined up yet for Pfizer’s infliximab biosimilar candidate, BioPharma-Reporter states. However, maybe this isn’t a surprise. According to consultant Elan Rubinstein, it might be more difficult for Pfizer to divest the candidate, given the current uncertainty of the market. Rubenstein says:
If you’re a payer and an unknown maker comes at you with a biosimilar product — and you’re already nervous about the category and whether patients and doctors will accept it — you’re more likely to buy it if it’s a Pfizer or an Amgen rather than an unknown name. The name factor gives people comfort in this unknown category. That kind of thinking could limit who could take the product.
My bets are on Allergan. It’s already rumored to be looking at making some more acquisitions to grow its biosimilar pipeline outside of the cancer space. Earlier in August, it was rumored to be looking at Epirus to pick up a biosimilar version of Remicade. It could be a prime candidate to buy up Pfizer’s version.
According to Forbes, generic drugs and biosimilars are poised to gain significant market share in some secondary markets. In particular:
Biosimilars are continuing to have strong growth and approval around the world. While Europe led the way, China’s market has become one of the world’s soundest due to the aging population, low insurance rates, and approval processes that are less restrictive than those in the U.S. This will also likely occur in countries like Russia as the government places limitations on imported drugs.
There’s been a lot written about China and its role in pharma innovation recently. The country has long been known for its process innovations, which enable quicker and cheaper manufacturing. It’s perhaps this fact that makes me less surprised to hear that the country would be more willing to embrace biosimilars. But despite the fact that approval processes are “less restrictive,” I’ve read that countries with drugs awaiting approval could have to wait for upwards of six to eight years before they receive the verdict. This long waiting time could slow the growth of the biosimilar market considerably.
Yesterday, the FDA released its guidance on the naming of biosimilars, proposing that each biosimilar name consist of the generic name and a four-letter suffix to help track adverse events. While this solution, modeled closely after WHO’s proposal, is a sort of compromise between brand makers and generics makers, FierceBiotech quotes Bernstein’s Gal Ronny saying:
We’ll be shocked if the innovative industry, notably those with products at near-term biosimilar risk (like Amgen and AbbVie, do not fight this. Their argument would be that the FDA is not going far enough in requiring different suffixes, and should require different generic names to protect the public.
Both sides had to compromise, sure. But the fact biosimilar names are going to be differentiated from the reference product via the suffix makes the reference product makers the bigger winners here (though perhaps not in market share — see my post below). I agree with Ronny here though; we certainly haven’t heard the last of this issue.
Will Biosimilars Naming Plan Promote More Competitive Drug Pricing? (8.27.15)
Modern Healthcare poses this important question in its headline following the release of the FDA’s proposal for biosimilar names. So, imagine my disappointment to discover that the author doesn’t even address this question in his article. He’s not a fortune teller, but he doesn’t even venture a guess. I’d say the answer is yes, and perhaps this is one area in which generic drug makers have won against brand makers. While biosimilars will have a suffix attached to the end of the generic name, setting them apart from the reference product, the fact they share the same generic name does make them appear more biosimilar. The closer they are in name, the closer a biosimilar becomes to its reference product and the more likely they are to be prescribed.
Bass IPR Poses Challenges To Enbrel: Good For Biosimilars? (8.26.15)
The legendary (or approaching legendary) hedge fund manager Kyle Bass, owner of Hayman Capital, has tacked a new target into its already-lengthy list of Inter Partes Review (IPR) challenges. This time around, Bass has filed a petition for IPR against one of the patents protecting Amgen’s biologic Enbrel. According to Seeking Alpha, this new challenge stands apart from the others in a few ways:
First, it is likely the biggest selling drug (approximately $5 billion per year) that Bass has attacked yet, with the exception of Celgene’s Revlimid. Second, while Bass has focused primarily on small-molecule drugs to date, Enbrel is the first biologic to be attacked.
It’s important to keep in mind that drugs have multiple patents protecting them from generic competition. Bass has yet to challenge all existing patents for drugs, and the ones he challenges are not often the most important patents affecting a drug’s market exclusivity. But if Bass is moving forward into the realm of the biologics, this could be helpful to companies like Sandoz that are looking to get their biosimilar candidates to market sooner than 2030. (On a side note—I just put together a Q&A with two patent attorneys for Life Science Leader about the growth of the IPR process challenging pharma patents, if you’re interested in learning more about this concept.)
Lantus Biosimilar Launched In U.K. (8.26.15)
Eli Lilly’s and Boehringer Ingelheim’s biosimilar Abasaglar, administered via injection in a cartridge or pen injector, is now available in packs of five for 35.28 Euros, PMLive reports. (Compare this to Sanofi’s reference product Lantus which sells for 41.50 Euros.) Sanofi is still trying to defend itself with its newest addition to the market, Toujeo:
For Sanofi, the increased competition to Lantus increases the urgency of its efforts to switch patients to Toujeo, a longer-acting version of insulin glargine which…has just been launched in the U.K. at the same price per day as Lantus. While still early, the French pharma major says switching to Toujeo is gaining momentum thanks to a strong label claim versus Lantus.
I think in order for this to work, Toujeo is going to have to gain the same amount of buzz and acclaim that Gilead’s Harvoni did after Sovaldi’s success. So far, I’m not hearing the same amount of buzz that Sovaldi/Harvoni got — and indeed, are still getting.
Study: Biosimilars To Have Small U.S. Market Impact (8.26.15)
A new AbbVie-commissioned study has revealed that biosimilar cost-savings will be less than other analysts have been predicting. These findings, however, were met with skepticism from biosimilar maker Sandoz. According to BioPharma-Reporter:
Despite the report’s findings, Sandoz believes that the savings opportunity over time for the U.S. healthcare system can be substantial. ‘The fact is that these products will bring much needed competition,’ spokesman for [Sandoz] Sreejit Mohan told BioPharma-Reporter. ‘As the first biosimilar nears the market, we have seen an uptick in these kinds of publications.’
And the war between brand and generic makers continues — this time through commissioned reports. Though I’m sure cost-savings have been over-estimated, or at least will take longer to be seen, I still find this to be a bit fishy. Seems a bit defensive, don’t you think?
Hospira mAb Biosimilar Flagged As Equivalent By PBAC (8.25.15)
Australia’s Therapeutic Goods Administration (TGA) has approved Hospira’s infliximab biosimilar Inflectra as the country’s first mAb biosimilar to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, adult/pediatric Crohn’s disease, refractory fistulising Crohn’s disease, adult/pediatric ulcerative colitis, and plaque psoriasis. However, while Australia already has nine approved biosimilars, Frost & Sullivan healthcare consultant Sanjeev Kumar told BioPharma-Reporter that Australia lags behind other countries in launching biosimilars because:
Australia is a relatively small pharmaceutical market. Despite having a good track record in biomedical research and a sound reputation in producing high quality biological pharmaceuticals, the country has a small generic and biosimilar medicine market. This is not very lucrative for the big pharmaceutical companies.
The country could be facing a change though; the Pharmaceutical Benefits Advisory Committee (PBAC) recently moved to apply an “a” flag to Inflectra. In other words, the PBAC has granted pharmacists the right to substitute the biosimilar for the reference biologic in cases where the doctor has not checked the “no substitutions” box. Marking a biosimilar as equivalent no doubt will improve the likelihood that the biosimilar will gain more prominence in the country.
5 Forces Impacting The Biosimilar Pipeline (8.21.15)
Richard Mark Kirkner for Drug Topics put together a great article, interviewing Aaron Gal, PhD., Sanford C. Bernstein & Co., on the forces at play on the biosimilar market. A couple of snippets for you:
Gal noted another positive sign for acceptance of biosimilars in the E.U. ‘Each successive product in the European Union did better than the earlier one,’ he said. ‘Payers, administrators, and hospital pharmacy chiefs in the EU are now largely convinced about the value of biosimilars.’
The biggest risks for the biosimilar market are obsolescence, he said, citing the example of Roche’s Lucentis (ranibizumab), and the extent of the competition. “We do not believe that in most drug/market combinations, differentiation between biosimilars will be an effective strategy,” Gal said.
In the U.S., Sandoz holds the glory of being the first to market, but maybe competitors need to look at it in a different way — Sandoz is going to warm up the market, taking the brunt of the industry’s skepticism and easing the way in for the rest of the players.
I’m also struck by Gal’s second quote here. Seeing all the consolidation happening in the generics market, I’m kind of suspicious now that, if differentiation between biosimilars won’t work out, we will actually see a similar amount of consolidation once the market becomes more established. Overall, this article is a goldmine of good information. Check it out!
Samsung Making Moves To Strengthen Biosimilar Joint Venture
The Wall Street Journal reports that Samsung is planning to list its biotech affiliate Samsung Bioepis on Nasdaq for $1 billion. The company is currently at work on six biosimilar products and is also working with Merck as well as Biogen Idec to develop and commercialize biosimilars. According to WSJ:
The listing of Samsung Bioepis Co. on the Nasdaq Stock Market will allow the company to raise money as it pours billions of dollars into research and development and production facilities to tap into the nascent and fast-growing field of biosimilars.
I like BioPharma DIVE’s term for what this could mean: “Biosimilar Behemoth.”
Who Could Allergan Target To Bolster Biosimilar Business? (8.20.15)
Bidness, etc. is speculating about the directions in which Allergan could choose to move following the sale of its generics division. One possible direction is making some acquisitions to bolster its biosimilar division. These acquisitions could include:
Pfenex,[which] could offer Allergan a range of biosimilar candidates in preclinical and clinical stages. Allergan is developing biosimilar cancer drugs while Pfenex produces biosimilars for non-cancer biologic drugs. Allergan has two biosimilar drug candidates in its pipeline. To improve on this, it could buyout Epirus Biopharmaceuticals…Epirus is developing three biosimilars for rheumatoid arthritis drugs Humira, Remicade, and Actemra.
Keep your eyes on these guys. Acquisition-hungry Allergan would be crazy to let the biosimilars market out of its sights.
Celltrion Challenges Rituxan Patents (8.19.15)
Celltrion has turned to the new “Inter Partes Review” (IPR) process to challenge patents protecting Genentech’s Rituxan rituximab, indicated for rheumatoid arthritis patients that don’t respond to tumor necrosis factor (TNF) alpha inhibitors, BioCentury reports.
In the petition, Celltrion alleged that all 14 claims of U.S. Patent No. 7,976,838 are unpatentable on grounds of obviousness. The patent was issued in 2011. …Celltrion argued that Genentech's claims were anticipated by prior art, asserting that trials prior to 2003 had studied methods for using rituximab to treat non-responders to TNF alpha inhibitors. The petition said about 40 percent of RA patients do not respond to anti-TNF alpha therapies.
I just did a Q&A for Life Science Leader about this very process. No doubt we’re going to be seeing more biosimilar companies challenging patents via the IPR process in the near future.
Ongoing TPP Negotiations Remain Threat To Biosimilars (8.18.15)
According to BioPharma-Reporter, the U.S. and Japan are continuing to fight with Australia, Canada, Chile, Peru, and other Trans-Pacific partnership (TPP) nations over IP protection for biologics. Many of the TPP nations are fighting against the proposed 12 years of biologic exclusivity, in favor of zero-, five-, or eight-year exclusivity period instead. BioPharma-Reporter says one Doctors Without Border representative believes:
‘The worst-case scenario’ for biosimilar access is an agreement to stagger the start times of data exclusivity periods according to when a biologic first launches in each country. In this case, if a pharma company markets a biologic in the U.S., and launches it in Peru some years later, Peru’s period of data exclusivity will begin with the Peru launch and not the American one. This means rival biosimilars will be delayed from filing in Peru, even if the original patent has run out.
Awesome. (Not.) This would not only be one giant headache to keep track of, but it also absolutely strays from the ongoing attempts between global regulatory bodies to streamline regulatory proceedings to ensure the quickest access to meds and a unified pharma industry. I have a feeling Sanofi’s head of R&D Elias Zerhouni would have some things to say about this, given his outspokenness in the past about the need for more harmonization in pharma.
Off-Label Uses Argument Good For Biosimilars? (8.14.15)
A judge in New York is claiming that the FDA’s attempts to keep pharma companies from making off-label claims about their medications goes against the First Amendment, says The Wall Street Journal.
The Second Circuit held that “the truthful promotion” of off-label uses is constitutionally protected speech that the FDA can’t regulate. The off-label speech prohibition ‘paternalistically’ interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public’s detriment, informed and intelligent treatment decisions.
This is a good start. Thanks to this, biosimilar makers could be free to extrapolate to their hearts’ content (as long as they have the data to back it up).
Neulasta Poses Bigger Challenge To Biosimilar Competition (8.14.15)
According to The Motley Fool, Amgen’s seeing success with its new Neulasta on-body injector:
The Neulasta on-body injector — which allows patients to be injected with Neulasta in-home rather than returning to the hospital or outpatient setting a little more than a day after chemotherapy treatments — appears to be hitting home already with physicians and consumers. The added convenience of its on-body injector has already led to 8 percent market share of its Neulasta business in Q2 during its first full quarter on the market — Neulasta generated $1.16 billion in sales — and its penetration is only expected to grow as Amgen highlights its benefits.
Biosimilar makers beware — Amgen’s onto something here. This doesn’t bode well for winning patients over to the biosimilars market if branded drugs keep getting more patient-friendly. For instance, Apotex is currently facing a lawsuit from Amgen, which could push back Apotex’s Neulasta biosimilar at least another year. This would give Amgen more time to win patients over with the on-body injector. Is Humira next? (Reminder…AbbVie is already thinking about this strategy.)
Doctor Biosimilar Education Seriously Lacking (8.13.15)
According to a recent survey by QuantiaMD, primary care physicians need a lot more education on biosimilar treatments, Medical Marketing & Media (MM&M) reported. According to MM&M:
While 78 percent of the doctors polled said they were familiar with the term “biosimilar,” only 38 percent could name a biosimilar that's under consideration for FDA approval that would be relevant to their patient population; only 33 percent could name a biosimilar at all… Only 17 percent of [120 ‘prescribing specialists’] said they are ‘very likely’ to prescribe biosimilars and 70 percent said they either aren't sure or are “somewhat likely'” to prescribe a biosimilar.
If this industry is going to take off, pharma needs to step up its game and get these docs some safety and efficacy information. There’s been a lot of chatter lately because of AbbVie’s petitions to get the FDA to change its labeling policy for biosimilars. Instead of just leaving docs to go to the purple book to access interchangeability information and comparative data, AbbVie wants all this info included in the label. I can see the benefits of both sides of this argument, but AbbVie’s solution could, to some extent, help boost doctor education and transparency.
South Korea Gains More Biosimilar Territory (8.13.14)
According to The Korea Herald, South Korea’s Celltrion has earned approval and can now begin selling its Remsima (Remicade/infliximab) biosimilar in Australia. The company is expected to flourish in the Australian market and is being eyed as a key bringer of competition to Roche, AbbVie, Novartis, Pfizer, J&J, and other big biopharma players because of its focus on biosimilars. The Korea Herald states:
The Korean government has been stepping up its efforts to support the nation’s biosimilar industry as a future growth engine. Earlier this month, the ICT and health ministries announced plans to inject 40 billion won into nurturing high-tech biopharma firms over the next three years.
Just a little bit more information for those of you looking to follow South Korea’s rise in the biosimilars space.
Congress: Don’t Treat Biosimilars Like Generics (8.12.15)
Thirty members of Congress have submitted a letter to the Centers for Medicare & Medicaid Services arguing against the current plan for biosimilar reimbursement, BioPharma Reporter says. According to the representatives:
[The Social Security Act] states that the calculation for reimbursing biosimilars shall be made separately, such that each biosimilar will have its own unique payment rate and unique HCPCS code…[the BPCIA created] a multi-tiered system of biologics and biosimilars as well as the possibility that multiple biosimilars to a single reference product may not share all indications. This CMS proposal may lead to confusion in each of these areas and dramatically reduce the investment in the development of biosimilars and thereby reduce treatment options available to patients.
If biosimilars end up with their own payment rates, etc., it seems like the next natural step is to give each biosimilar its own unique name.
Data Exclusivity: An Attack On Science? (8.11.15)
In his column on Techdirt, Glyn Moody argues:
Although dressed up in terms of fairness and recouping investments, the very notion of data exclusivity is an attack on the key idea that no one can own a scientific fact, and that science advances by building on existing knowledge…The only acceptable length for data exclusivity is zero years; anything longer turns TPP into an attack on science itself.
This is a really interesting take I hadn’t thought about.
Novartis To Buy Pfizer’s Remicade Biosimilar? (8.7.15)
Bidness, etc. has speculated that Novartis’ generics powerhouse Sandoz could be considering scooping up the rights to Pfizer’s biosimilar of Johnson & Johnson’s Remicade.
According to a survey conducted by Bloomberg Intelligence, the most successful biosimilar drugs would be the copycat versions of Humira, Neupogen, Remicade, Neulasta, Epoitin-alfa, and Enbrel. This indicates that Sandoz is already developing all of the biosimilars which are expected to be the most successful in the U.S., except the biosimilar version for Remicade. It is likely that Novartis would become interested in acquiring Pfizer’s infliximab biosimilar, which is also in its late-stage clinical trial, to get all the biosimilar drugs which can potentially be the most successful.
It will be interesting to see if this happens.
Dr. Reddy’s Sets Sights On U.S. Biosimilars Market (8.7.15)
Dr. Reddy’s recently announced its intentions to set its sights on growing its generics and biosimilars businesses. CEO Neha Bothra told Financial Express:
Biosimilars will take some time to scale up in terms of revenues. At present, they are $50 million or so. As we register our products in various markets, we will see revenue growth. Our big revenue market will be the U.S., where we have partnered for the first few assets and will earn revenue streams from that.
Looks like Dr. Reddy’s has faith in the potential of the U.S. biosimilars market.
Biotech Boasts New Biosimilar Manufacturing Procedure (8.6.15)
MedCity News has profiled New Hampshire biotech Avitide, which recently gained funding to build a platform to help those making biologics and biosimilars construct unique molecular structures more efficiently.
The company uses affinity purification to develop what it says is a highly precise biologics manufacturing system – separating out impurities that were previously impossible to remove, [CEO Kevin]Isett said. One application of Avitide’s drug manufacturing platform: It can help pharmaceutical companies create complex, hard-to-duplicate biologics. But the company’s also able to help biosimilar clients reverse-engineer existing biologics on the market…
It’s just a start-up, so we probably should check our expectations that this will ultimately bring about a quicker process to developing biosimilars. Nonetheless, it’s still an interesting concept.
Back To The Basics: How Humira Got Its Start (8.6.15)
The U.K. BioIndustry Association put forth a blog highlighting the history of Humira and how it got its start in the U.K. While Humira is a huge success now, like most wonder-drugs, the path to market had some roadblocks, including restructured partnerships and royalty disputes. However, the blog also unpacked some of the science behind Humira’s original discovery:
Key to Humira’s discovery was the “phage display” method. This uses special viruses called bacteriophages as vehicles to display proteins of interest on their outside, so they can be screened for interactions with other proteins or molecules. Antibody “libraries” containing millions of different human antibody fragments displayed on phages are thereby used to isolate very targeted, specific leads with therapeutic potential. These fragments are then used to build full-sized antibodies using humanization technologies.
I think it’s good to take a step back and think about the basic science behind a drug that has become as commercially successful as Humira — especially these days as industry R&D dwindles and so many important scientific discoveries remain unnoticed due to lack of funding.
Pfizer To Divest Remicade Biosimilar (8.6.15)
The European Commission has blessed the Pfizer-Hospira merger, but with some conditions relating to the two companies’ development of biosimilars. According to BioPharma-Reporter:
The Commission said rival pharma companies would not provide enough competition against the merged company, risking Pfizer increasing its prices or discontinuing development of its infliximab biosimilar… in order to focus on Hospira’s Inflectra (developed by Celltrion), leading to an uncompetitive market.
So, who is going to end up with Pfizer’s biosimilar?
Will Longer IP Protection Actually Hurt TPP Nations? (8.5.15)
For those of you paying close attention to the Trans-Pacific Partnership (TPP) negotiations, IPWatchdog posted an opinion piece called “The Sticking Point That Shouldn’t Be: The Role Of Pharmaceutical Patents In The TPP Negotiations.”
Anti-TPP activists argue that this protection, and pharmaceutical data exclusivity in particular, will increase costs and create a barrier to wide-reaching access to medicines. However, there are good reasons to doubt this. First, the majority of the negotiating nations are well-developed. Moreover, trade and IP protection enhance economic growth and development, which enhances access to medicines. The nations currently negotiating the Trans-Pacific Partnership Agreement are all classified as ‘High-income’ or ‘Upper-middle-income’ with the exception of Vietnam, which is considered ‘Lower-middle-income’ (World Bank). The protections within the TPP Agreement will only enhance the development and growth that characterize these nations.
Food for thought here. I wasn’t aware of the breakdown of each country’s economics. However, I’d be interested in digging into this further, because at the end of the day, the high income countries aren’t a surprise: Australia, Canada, Japan, New Zealand, Singapore, and the U.S. But economically and medically speaking, the terrain has to be different in the middle income countries of Chile, Peru, Malaysia, and Mexico compared to, say, the U.S.
5 Unanswered Questions About Biosimilars (8.5.15)
Deloitte made a list of five unanswered questions biosimilars companies should consider before entering the market that could be a “gold mine for major pharma companies.” These questions include: Can the business afford it? What state and federal mandates could stand in the way of the market’s growth or expansion? What is the organizational appetite for investment? What kind of pricing structure needs to be put in place? Will we experience the level of consumer discounts long associated with the growth of generic drugs?
I have a feeling tackling the pricing structure to ensure return on investment will be one of the biggest hurdles here. I’m thinking, too, of the advice to target biobetters instead of biosimilars from Dentons discussed below in this thread. Deloitte expects the leap into the biosimilars market won’t be an “insurmountable” challenge for branded pharma companies, however the firm cautions smaller companies that might have smaller margins. Makes sense.
Shire Makes Move To Buy Baxalta (8.5.15)
Shire has made a $30 billion bid for Baxter’s spinoff company Baxalta — a move which would make the combined company a leader in the rare disease space. The fledgling company however, has already turned down the offer in favor of focusing on treatments for cancer, hematology, immunology, and biosimilars, The Boston Globe reported. In fact, according to the Motley Fool, Baxalta and partner Momenta are working towards a biosimilar of Humira:
Momenta is expecting data for its first biosimilar, a copycat of AbbVie's Humira, in the fourth quarter and expects to start a larger patient study this year. If all goes well, Momenta and partner Baxalta will be able to gain approval in 2017 and launch in 2018.
I’m curious then, if Shire manages to woo Baxalta with a higher offer, what might come of its work in the biosimilar realm? Will it continue?
Amneal Ups Biosimilars Game With Revamped Ireland Facility (8.3.15)
Amneal Pharmaceuticals has swooped in on a former Johnson & Johnson plant in Tipperary, Ireland, FiercePharmaManufacturing reports. Amneal, which has garnered a reputation as the seventh largest producer of generics, has expressed its intentions to use the new manufacturing facility “for R&D and production of metered dose and dry powder inhalers, as well as biosimilars.”
A bit of trivia for you — Amneal was named Company of the Year at the Global Generics & Biosimilars Awards 2014 last October. Who won the category Biosimilar Initiative of the Year? Might not come as a surprise — Sandoz carried off that trophy following the FDA’s acceptance of its filgrastim application for review.
Are Biobetters The Better Choice? (8.3.15)
John M. Clerici and Phillip Bradley of law firm Dentons put forth a column on the players in the life sciences industry that will benefit from the “current turmoil” of the U.S. biosimilars market. According to Clerici and Bradley, biobetters are likely to be a smarter investment at this point in time:
Innovators of biologics are likely to also be moving in this direction of bio-betters in response to price competition given that they are best able to leverage what is known about the core molecule, its clinical experience, any manufacturing challenges, and opportunities to decorate the molecule such that they can demonstrate superior health outcomes. This has the benefit for the innovator company of maintaining a portfolio of high price point products with superior activity compared to impending biosimilar market entrants.
There’s already talk of AbbVie upping its game with Humira. The company has created a less painful injection that could lead to smaller volume doses in the future, FiercePharma reported a couple weeks ago. But at the same time, this isn’t the first time biobetters have been proposed as a better option. In fact, back in 2010, The Wall Street Journal highlighted biobetters as a bigger opportunity — but at least in terms of media coverage, this option seems to take the backseat to biosimilars. I’m curious if this lack of focus isn’t indicative of the industry’s disinterest in pursuing biobetters over biosimilars at this juncture.
RA Market Lucrative Target For Biosimilar Makers (8.3.15)
At the 2015 Annual European Congress of Rheumatology conference, several companies presented data for their rheumatoid arthritis and other autoimmune disorder biosimilar candidates. Data presented included that of Hospira’s infliximab (Remicade) biosimilar Inflectra and Samsung Bioepis’ SB4 (etanercept/Enbrel), SB2 (infliximab/Remicade), and SB5 (adalimumab/ Humira). According to BMI Research, the data demonstrated that:
Whilst still very much in its infancy, the biosimilar market is gaining shape and traction, particularly with regard to RA products. This is a potentially very lucrative area for biosimilars given the larger patient population and the fact that biologics for conditions such as RA tend to have indications covering a wide spectrum of autoimmune conditions.
Good to know.
Trastuzumab Resistance Opens Door For New Treatment Options (8.3.15)
Trastuzumab, one of the biologics facing patent expiration in the U.S. in 2019, is being widely targeted by biosimilar makers. However, 15 to 25 percent of breast cancer patients face trastuzumab resistance. In a Q&A with BioMed Central, Amir Sonnenblick, a research fellow at the Breast Cancer Translational Research Research Laboratory, Institut Jules Bordet, Universite libre de Bruxelles, explains the implications of this resistance:
We propose that the IL6-STAT3-stromal feed-forward loop… is predictive of trastuzumab resistance. Therefore, inhibiting the IL6-STAT3 pathway may be a valuable addition to trastzumab treatment of HER2-positive breast cancer… There are few IL6-Jak-STAT3 monoclonal antibodies and tyrosine kinase inhibitors in different stages of development… The U.S. Food and Drug Administration have approved siltuximab (anti IL6 monoclonal antibody) and tocilizumab (IL-6 recpetor blocking antibody) in multicentric Castleman’s Disease. Tocilizumab as well as JAK inhibitor are also used to treat rheumatoid arthritis. It would be intriguing to evaluate these drugs in the treatment of HER2 positive breast cancers.
Fifteen to 25 percent of the breast cancer population isn’t a huge percentage, but certainly worth taking note of — especially in terms of potential competitors in the space — for those developing trastuzumab biosimilars.
Biocon Generics Push Expected To Foster Biosimilar Development (8.3.15)
An article in Livemint profiles India’s largest biotech Biocon, which, next to Dr. Reddy’s, has earned the reputation in India for being one of the only two companies investing heavily in biosimilar development. In latest news, the company has decided to enter the U.S. generics market:
“For Biocon, ramping up the Abbreviated New Drug Applications (ANDAs) side-by-side [to biosimilar development] is a piggyback where they can incrementally and directly participate in the market…This will be a fallback mechanism for Biocon as they have burnt a lot of money on biosimilars research, and the bioequivalence and bioavailability (acceptability of a drug with patients biologically) studies are not established yet. The company has perhaps now realized that they cannot keep burning money into research and need a stable stream of revenue as well,” said UBS analyst Hemant Bakhru.
Interesting perspective here. It seems particularly significant considering the fact that big companies like Allergan and Boehringer Ingelheim took the plunge and sold off their generics businesses in recent weeks.
South Korea Establishing Reputation As Biosimilar Goliath (8.2.15)
According to The Korea Herald, South Korean pharmaceutical companies are lagging behind their global pharma peers in terms of patents for new product development. The Herald reports:
Of the 1,754 patents filed in Korea since official monitoring began in March 2012, 1,310 were by international pharmaceutical companies whereas only 444 came from local firms… Industry watchers say that compared to their global counterparts, Korean pharma firms lack the level of capital and technology needed to more actively drive forward research required for product development and commercialization.
South Korea might not be a leading force in R&D of new drugs, but they’re on the map for biosimilar development. The country boasts the largest number of biosimilar clinical trials and biosimilar pipeline targets, according to CPhI.
JAMA Highlights Proposed Biosimilar Traceability Solutions (7.31.15)
In a recent blog post, Peter Wehrwein discusses an opinion piece published in JAMA by Amitabh Chandra, director of health policy research at Harvard’s Kennedy School of Government, and Jacqueline Vanderpuye-Orgle, director of research operations at Precision Health Economics. According to Wehrwein, the authors argue:
At least some of the reluctance of physicians could be overcome…with ‘traceability,’ which they defined as ‘the process of tracking a particular dose to a specific manufacturer, facility, and manufacturing batch.’… Another plank in Chandra and Vanderpuye-Orgle’s traceability platform is that it would help with formulary design and cost-sharing because identifying a biosimilar as a biosimilar means it can be priced different and offered on a different (presumably less expensive) tier than its brand-name counterpart.
Interesting points here. They offer a few different solutions, including adding an identifying code after the name (like the WHO proposal), using National Drug Codes (10-digit numbers that identify the labeler, product, and package size), or using postmarket surveillance to determine bioequivalence, and therefore an appropriate naming system.
5 Issues To Watch In Biosimilar Legislation (7.30.15)
The National Law Review posted some information on emerging state biosimilar laws and five issues to watch. Theresa Carnegie, Joanna Hawana, et al. of Mintz, Levin, Cohn, Ferris, Glovsky, and Popeo, P.C. write:
Three states require the pharmacist to substitute the biosimilar product unless certain criteria are met. For example, in Tennessee, the prescriber must satisfy fairly strict standards to demonstrate that the prescribed biological product is medically necessary for the particular patient in order to prevent biosimilar substitution… It will be interesting to see whether any other states take a similar approach to Tennessee’s unique requirement that the prescriber demonstrate medical necessity in order to prevent substitution of the biosimilar.
Something to keep in mind here — this could cause a limit in demand.
Merck Remicade Sells Feel Biosimilars Pinch (7.29.15)
The Remicade biosimilar that hit the European market in February might not be affecting AbbVie’s Humira sales, but it sure sounds like Merck, which markets Remicade in Europe, is feeling a pinch. According to The Wall Street Journal:
Merck officials said Tuesday the company has had success convincing European health systems and doctors to keep existing Remicade patients on the drug. But new patients are being steered to the biosimilars, Merck said. ‘Over time, we believe that as more new patients come into the market, we will lose market share,’ Adam Schechter, head of Merck’s drug-marketing unit, told analysts on a conference call.
Sounds like J&J CEO Alex Gorsky was right in his prediction that doctors would keep their patients on the brand-name drug…for now.
Acquisition-Hungry Allergan Eying Biosimilar Giant Amgen? (7.28.15)
Rumor has it Allergan is hungry for more acquisitions after pitching its generics division to Teva. Bloomberg Business reports that:
The Teva transaction lets Allergan pay off debt from its $66 billion combination with Actavis, allowing it to build its brand-name medicine business with small deals or to pursue larger acquisitions such as Amgen or AbbVie, said Ken Cacciatore, an analyst with Cowen & Co. in New York.
So, if all goes as Cacciatore expects, Allergan could end up wresting its biosimilars partnership/candidates with Amgen out of Teva’s grip. Teva might’ve gotten a stronger foothold in the generics business, but its biosimilar division could continue to remain “selective,” to say the least. Not to mention, in 2013, Thomson Reuters forecasted that Amgen would be one of the dominant players in the U.S. biosimilars market. An acquisition of Amgen could someday make Allergan a key player in the biosimilar market.
Creating Brand Identity For Biosimilars (7.27.15)
Even though it’s over a year old, PMLive’s blog posting about how to create a brand identity for biosimilars on the market still holds value, especially considering the recent negotiations over how biosimilars should be named. As PMLive writes:
It’s important to promote biosimilars as brands in their own right, not generic copies. Though biosimilas have to match the reference product in terms of quality and performance, it’s essential to highlight any additional benefits they offer. Building a value proposition may involve steering away from the branded predecessor and promoting the biosimilar as something new with distinctive supplementary features or services (such as state-of-the-art production values).
If the industry moves in the direction of WHO’s compromise that a biosimilar’s name be the same with only a four-letter identifier tacked onto the end, companies might run into some difficulties emphasizing their biosimilar as an equal and valid competitor against the reference product.
AbbVie CEO Says Biosimilars Not Cause Of Humira Sales Slump (7.24.15)
International sales for Humira are troubled, according to BioPharma-Reporter. But are biosimilars for Remicade the problem? They’re not, according to AbbVie CEO Richard Gonzalez who is blaming a shipping issue. BioPharma-Reporter quotes Gonzalez:
The first quarter international growth rate of nearly 15 percent was favorably impacted by the timing of shipments in select markets. Consequently, international sales growth in the second quarter was negatively impacted by the shipment timing…We measured every one of those markets that [biosimilars for Janssen’s Remicade] are in; we’ve been doing it from the very beginning, and in those markets, Humira continues to grow as we would have expected it. We don’t see any impact from, nor did we expect any impact from Remicade biosimilars within those markets.
Maybe… But if Remicade got hit pretty hard by infliximab biosimilars, and all Humira has over Remicade is the polyarticular juvenile ideopathic arthritis indication, I’m finding this a little hard to believe.
Could A New Formulation Save Humira From Biosimilar Competition? (7.24.15)
There’s nothing a new formulation can’t solve! According to FiercePharma:
AbbVie recently won European approval for a new formulation of the drug. The improved version cuts down on the pain patients feel upon injection, a characteristic AbbVie hopes will improve adherence. It may allow the company to ultimately cut down on the volume of the injection down the road, too, Gonzalez said. ‘We do think it’ll be differentiated,’ he noted, predicting a future ‘material impact’ on Humira’s performance.
I guess the question then becomes will an easier, less painful formulation win over a cheaper price? If doctors remain hesitant about straying from the norm, probably. But given today’s pricing pressures from payers, I’m betting price will be the ultimate winner in the end. There’s also no saying that some of the new players entering the market won’t end up playing around with this idea themselves.
Anna Rose Welch
Anna R. Welch is the editor of Biosimilar Development, covering the development, manufacturing, regulatory, and industry issues related to Biosimilars. She also serves as an associate editor for several Life Science Connect properties, including Bioprocess Online, Clinical Leader, Outsourced Pharma, and Pharmaceutical Online.
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