By Anna Rose Welch, Director, Cell & Gene Collaborative
I know, I know — I normally only do the top five developments for the biosimilar industry in this annual column. But it turned out, upon reflection, that 2019 was an even more eventful year than it may have seemed as we were making our way through. So, you’re getting a whopping seven this year. (Merry, merry!)
After the past year, I’d venture to declare that the industry — especially in the lagging U.S. market — is growing healthier by the day. That’s not to say, however, that there aren’t still significant barriers and challenges facing the industry in the year ahead. This article may not be written in iambic pentameter, rhyme, or be composed to the tune of 12 Days of Christmas like one ambitious editor chose to do for their end-of-year wrap-up (show-off). But this column remains one of the most popular articles to be published on Biosimilar Development from year to year, and it is always one of the most fun to write. Enjoy — and, as always, I’m happy to hear your thoughts, comments, and additions in the comment section below!
7. World Health Organization A Central Player In 2019
It’s only been a year and some months since the WHO accepted its first dossier for its list of prequalified biosimilar medicines. Though this announcement was followed by silence and whole heck of a lot of intrigue, there has been quite a bit of progress made for just a year. In fact, we just celebrated the news that the WHO has officially prequalified its first biosimilar Herceptin (made by Samsung Bioepis). Having heard a presentation from one WHO technical officer a few months ago at a conference, I can appreciate this approval so much more because of the amount of work it took to establish the two different prequalification pathways (i.e., full and abridged). Though WHO started biologics prequalification with biosimilars of trastuzumab and rituximab, the organization also announced it is broadening prequalification efforts to include insulins. (It doesn’t specify in the press release whether this effort will include biosimilars or be limited to innovative drugs.) Just as those of us in the U.S. have been paying close attention to the insulin space because of the March 2020 FDA regulatory transition, we can also anticipate more efforts related to insulin access from the WHO in 2020; as the press release specified, the organization plans to update treatment guidelines, which will also include improving affordability and administration and monitoring methods.
I was particularly heartened to see such progress made, as it goes a long way to honor the memorandum of understanding signed by both the WHO and International Generic and Biosimilar Medicines Association in the fall. Given the conversations about the role biosimilars (and generics) have and can play in improving global access to treatment — especially in developing nations — I hope to continue hearing such news out of the WHO in the upcoming year.
6. Long-Awaited Competition Hits The Oncology Space, With More To Come In Early 2020
In July, we got word that Amgen had launched the first two cancer biosimilar mAbs onto the U.S. market — Mvasi (Avastin) and Kanjinti (Herceptin). It wasn’t long after those launches that we heard that several community oncology clinics had adopted these treatments and that UnitedHealthcare (UHC) had placed these biosimilars on the primary tier of its formulary. (After UHC’s decision to bump Coherus’ biosimilar off its primary tier in favor of Neulasta or Neulasta OnPro, this was certainly welcome news.)
These launches set off a string of other positive events, including the launch of Mylan and Biocon’s Herceptin biosimilar Ogivri and Pfizer’s launch announcements for its Avastin biosimilar (December 31, 2019), its Rituximab biosimilar (January 2020), and its Herceptin (February 2020).
There has also been some impressive movement for Neulasta biosimilars. Coherus’s Udenyca has been killing it, announcing in mid-July it had surpassed production of 400,000 vials of Udenyca. Though Mylan’s Fulphila has been on the market for even longer (since mid-2018), there has been little discussion of how competitive it’s been given supply concerns over the past few months. But why have two products in play, when you can have three? Sandoz’s FDA approval of Ziextenzo resulted in a quick market launch and a slightly deeper discount than we saw for that of Mylan’s and Coherus’ respective biosimilars. While both launched at 33 percent discounts to Neulasta’s wholesale acquisition cost (WAC), Sandoz has gone down by 37 percent.
Though we’ve grown used to the trials and tribulations of securing uptake and confidence in the autoimmune space, the oncology community seems quite excited by the newfound presence of biosimilars. In addition to a number of articles I’ve seen about biosimilar usage at the community oncology level, Kaiser Pemanente (KP) has also been reporting some stunning data surrounding its oncology biosimilar usage. Per one of KP’s physicians on Twitter, Mvasi, Kanjinti, and Truxima have hit 90 percent, 85 percent, and 87 percent respectively within the IDN. What’s even more impressive and telling about the upcoming year for these products: Truxima was just launched on November 7th.
5. Publications Targeting Global Biosimilar Regulatory Advancement, Alignment Abound
Last year, one of my top 5 developments of 2018 was the approval of two Neulasta biosimilar products without large-scale comparative efficacy studies. The excitement around this, of course, was that it showed us how development could play out in the future for a number of products. While we’re hardly close to this development model for the more complex biosimilar products, there has been no shortage of discussion this past year around how we can advance the development pathway.
For one, as we noted a few weeks ago, the FDA put forth an exciting guidance for future insulin biosimilars which, among many things, promotes much-needed alignment with the EMA around insulin clinical trial requirements. In addition, the concept of interchangeability switching studies appears to be eliminated for well-characterized insulins, which goes nicely hand-in-hand with the sentiment expressed in this article by Hans Ebbers: “Are We Ready To Close The Discussion On The Interchangeability Of Biosimilars?” It also jives nicely with this article by Fernando de Mora and company: “Biosimilar And Interchangeable: Inseparable Scientific Concepts?”
There were also some very welcome publications centered around the role of clinical trials in biosimilar development. For one, there was what I — a good Lutheran girl — termed the “Second Reformation,” in which Gillian Woollett and Chris Webster penned their urgent call to action to regulators to implement a new regulatory paradigm known as confirmation of sufficient likeness (CSL). At the core of this proposal was the fact that analytical comparability can tell us as much — if not more — about a biosimilar’s structure and function than large-scale efficacy trials.
After the last year, it would seem some of the more outspoken regulators are (generally speaking) becoming more comfortable with development paradigms in line with CSL. At the U.S. DIA Biosimilar Conference in September, the FDA’s Janet Woodcock repeatedly emphasized just how much we know about biosimilars today thanks to technological advancements and how this will give us the confidence to make the development pathway resemble that of small molecule generics. Taking it a step further, Elena Wolff-Holz of the European Medicines Agency published her own paper digging into the role of clinical confirmation trials and how heightened attention on the PK study could encourage future clinical data reductions.
4. Canadian Provinces Implement Sweeping Biosimilar Transition Policy
I’ve been watching Canada for a while, especially after hearing about one non-profit payer’s successful Remicade switching program, along with efforts from one patient advocacy group to instill confidence in the use of biosimilars across the country. But the truth of the matter remains that, following the British Columbia transition and the Alberta transition, there was a noticeable difference in opinion between different patient populations. While rheumatoid arthritis organization Arthritis Consumer Experts worked closely with the governments in each province to ensure a patient-centric transition, gastroenterology patient advocates and physicians have been speaking out adamantly against the transition, citing a lack of evidence in biosimilar safety and efficacy in IBD indications.
I imagine we’ll continue to see other provinces follow in BC’s and Alberta’s footsteps, and in 2020, I’m going to be watching for the release of a forthcoming stakeholder consultation process being carried out by the Canadian Agency for Drugs and Technologies in Health (CADTH). This project aims to deliver all stakeholder perspectives to the Canadian government so it can craft the most appropriate biosimilar policies for the country moving forward.
3. Proposed U.S. Policies Consider Much-Needed Stakeholder Incentives
I can only imagine for those of you looking in on the U.S. healthcare system right now, it’s been an overwhelming endeavor to keep track of all the policy and drug pricing proposals that have been proffered in the past year. (Frankly, I haven’t kept keep track of them all, either.) But rather than going into each and every single policy that’s been proposed, it’s most important to know that the policies being proposed are setting out create the necessary incentives for patients and physicians to embrace the biosimilar transition. Though there are increasing numbers of biosimilar competitors, in both the oncology and autoimmune space (Amgen should be launching biosimilar infliximab #3 at any point now), price competition isn’t quite as exciting as some may have hoped. In turn, patients and physicians may be underwhelmed by or not even realizing the savings that biosimilars are currently offering.
As such, the Biosimilars Forum has made lots of progress in promoting policies that will reduce out-of-pockets costs for patients taking biosimilars, implement shared savings programs for physicians, and create add-on payments to incentivize prescribing physicians. In an effort to encourage preference of the biosimilar on formularies, another policy aims to provide Star Ratings to payers in the Medicare program for their implementation of biosimilars on their formularies.
As it stands now, if passed, these policies would only impact patients under Medicare Part B, but it’s often said the commercial space follows in CMS’ footsteps.
2. Biosimilar Usage Improves In U.S. Community Oncology, Immunology Settings
Though it’s true that the U.S. has faced sluggish biosimilar uptake in the past few years, oddly enough, in 2019 we seemed to hear the exact opposite — there were quite a few voices proclaiming their success with biosimilars. In addition to hearing from the OneOncology clinics about using the new oncology mAbs Mvasi and Kanjinti, I was particularly excited to hear about the success the largest rheumatology practice in the U.S. had with a value-based pathway encouraging the use of infliximab biosimilars.
Though we focus more closely on the biosimilar successes of IDNs like Kaiser Permanente or on the troubles with uptake in larger health systems/hospitals, the past year has demonstrated that there is a whole world of physicians that are working within more intimate and (typically) more resource-constrained sites of care. Couple this with the ongoing push toward value-based care and the potential for shared savings in these programs (i.e., the Oncology Care Model), there is a natural push toward lowering the overall cost of treatment. This has made biosimilars a particularly appealing addition to the standard of care, and I only anticipate we’ll continue hearing from the community and independent practices about biosimilar uptake in 2020.
1. The Rise Of The Small Biosimilar Company
Biosimilars have not been an easy journey for any company, but it’s a truth universally acknowledged that smaller companies have faced even more hurdles than larger companies. (Funding, anyone?) This is why so many of the smaller companies that were leading players back in the early days have since gone on to innovative treatments, been snapped up by bigger players, or have disappeared from the industry all together. However, if 2019 proved one thing to us, it’s that there is still a thriving community of smaller companies working at biosimilar development.
For one, Coherus is kicking ass and taking names in the U.S. market with Udenyca (which had upwards of 20 percent of the market less than one year in). Moving forward, it will also be expanding its pipeline to include Formycon’s Lucentis biosimilar.
We’ve also heard from a few players that are setting themselves up to be stars in the next wave of biosimilar products to hit the market. In particular, Australian biosimilar pureplay NeuClone has announced the start of its Phase 1 trial for its Stelara biosimilar candidate. In addition to its Lucentis biosimilar, Formycon also announced that its own Stelara biosimilar has entered a Phase 1 trial.
Finally, I enjoyed reading this feature on pure-play company Xbrane, which is currently working on pre-clinical development of a biosimilar Cimzia and Opdivo in collaboration with STADA, and has preclinical programs for Oncaspar, Decapeptyl, and two other undisclosed biosimilars. Xbrane will potentially be a competitor against Coherus/Formycon’s Lucentis biosimilar, seeing as Xbrane’s own Lucentis biosimilar is currently in Phase 3 development.
Earlier this year, I wrote an article about NeuClone entitled “Biosimilars: Not Just Big Pharma’s Playground.” I anticipate this statement will become even more relevant as the next few years unfold.
Honorable Mentions (in no particular order)
The FDA approved its 26th biosimilar — Amgen’s Avsola, which will be the third infliximab biosimilar to launch (date TBD).
The International Coalition of Medicines Regulatory Authorities (ICMRA), which comprises the heads of 29 regulatory agencies, released a statement in support of biosimilar safety, efficacy, and quality, biosimilar use in clinical practice, and the overall regulatory review and approval process.
The FDA published its final interchangeable biologics guidance.
Fresenius Kabi announced a new biosimilar R&D lab for future oncology, immunology biosimilars.
Health Canada chose to stray from FDA naming policy and will not be adding non-meaningful suffixes to future or current biologics and biosimilar treatment names.
United States, Mexico, Canada Agreement (USMCA) eliminated the highly contested biologics exclusivity provision. Exclusivity will remain eight years in Canada and five in Mexico, as opposed to being increased to 10 years.
FDA held a Part 15 hearing on insulin biosimilars and interchangeable biologics to prepare for its March 2020 regulatory transition.
Sites of care in the U.K. continued to demonstrate success with gainsharing efforts following a transition to Enbrel.
Crohn’s and colitis patient and physician organizations strongly denounced the B.C. and Alberta Canadian transition programs.
Amgen launched two oncology biosimilars “at-risk,” but the district court of Delaware determined Genentech could not block the commercial launch. (Editorial board member Alexandra Valenti discusses this further here.)
One well-known analyst declared the U.S. biosimilar infliximab competition “essentially a failed market.”
FDA released a new guidance on comparative analytics to the industry’s delight. This guidance replaced the former guidance on statistical approaches to evaluate analytical similarity, which drew much industry ire in 2017.
Celltrion approved a subcutaneous version of its CTP-13 infliximab biosimilar in Europe for the treatment of RA. The “biobetter” is currently in trials for the treatment of IBD, with hopes for an EMA approval in mid-2020.
Former biosimilar pureplay Oncobiologics, now known as Outlook Therapeutics, announced that it is developing an innovative version of bevacizumab for retinal diseases typically treated off-label with Avastin. Neither the innovator nor its approved biosimilar versions are currently approved to treat retinal diseases.
Samsung Bioepis announced an extension of its biosimilar pipeline, along with an expansion of its partnership with Biogen in several European countries and China.
The American College of Rheumatology cautioned against transitioning to biosimilars in axial spondyloarthritis.
Brazilian biosimilar maker Libbs announced ANVISA’s approval of the first Brazilian-made mAb biosimilar, Vivaxxia (rituximab).
The Federal Trade Commission announced it is investigating J&J’s contracts with payers for Remicade, which Pfizer alleges included bundled rebates, in turn creating an anti-competitive environment for Inflectra.
In a series of back-and-forth debates, economists from the American Enterprise Institute went head to head with several authors from Memorial Sloan Kettering on whether it was time to “throw in the towel” on biosimilars.
Pfizer announced it is cutting five of its preclinical biosimilar programs.
Advisory firm Willis Towers Watson released a survey of 610 U.S. employers, which revealed that 30 percent of employers are incentivizing the use of biosimilars in their plan design. Over the next two years, we should see an additional 39 percent of employers implementing similar initiatives.
In two separate studies, switching between two different infliximab biosimilars (CTP-13 and SB2) did not cause any safety or efficacy concerns in IBD and psoriasis.
The FDA released a new suite of biosimilar educational documents for patients.
Amgen vs. Sandoz’s Enbrel biosimilar court case resulted in a win for Amgen, which could mean 30 years of exclusivity for Enbrel.
Boehringer Ingelheim settled with AbbVie, securing a 2023 U.S. launch for all Humira biosimilars. BI was the last hold-out for a court triumph and an earlier launch.
The discussion about biobetters — and particularly, oral formulations of existing biologics — continued to garner attention. Two stories grabbed my attention this year, the first being the use of microneedles for oral insulin, and the second being the creation of infliximab tablets for IBD.
The U.S. administration eliminated the proposed rebate Safe Harbor bill.
The Senate Health, Education, Labor, and Pension’s committee proposed legislation that incited more back-and-forth on a long-standing debate between the U.S. Pharmacopeia (USP) and the FDA on certain USP standards (monographs). The legislation has since been altered to remove language that could have effectively rendered USP standards null and void.
The breast cancer patient advocacy group Susan G. Komen released its first educational materials on biosimilars for patients just weeks before the first commercial launch of Amgen’s Kanjinti.
Biosimilar companies Amgen, Pfizer, Biogen, and Sandoz reported U.S. market growth of their launched biosimilar products.