By Anna Rose Welch, Director, Cell & Gene Collaborative
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Well, folks, it has been a Year. If you’re like me, you probably feel as though you’re limping to the finish line of 2020 and hoping for some sense of normalcy to return as early as is safely possible in 2021. Though 2020 felt like an endless descent into Dante’s Nine Circles of Hell, I wanted to end the year as I typically do: with a column highlighting the most important and positive biosimilar developments from the past 12 months.
From year to year, it becomes increasingly challenging to pick individual events of note. Rather, each seemingly independent event ties together to create larger movements in the global biosimilar industry. It goes without saying that COVID-19 was a huge disruption to the healthcare and pharmaceutical industries, as well as to our personal and professional lives. We will continue to feel the pandemic’s impacts for some time. But I daresay some positives will (and have already) come out of these upheavals, especially in the biosimilar space. As healthcare systems seek immediate financial relief, these amazing treatments are finally getting the attention and utilization they — and, most importantly, patients — deserve.
On a more personal note, I’m sad to say that this will be one of my last Biosimilar Development columns. I am transitioning into an exciting new editorial role in the cell and gene therapy manufacturing and outsourcing space. The past five years of living in the biosimilar industry alongside you have been an immense joy. It has been a journey I could never have anticipated back in 2015 when I told my supervisor I’d Google what biosimilars are and see if I could write something about them. I thank you all for your readership and your leadership in moving this essential industry forward. Keep up the good fight, and please keep in touch. I wish you all a happy and healthy new year!
5.) U.S. Policy Proposals Take A Page From European Successes
Though the U.S. government was distracted (to say the least) by the pandemic and November’s election, the biosimilar industry has fought to keep biosimilar-friendly reimbursement schemes on legislators’ wavelengths. In addition to advocating for Medicare Part B reimbursement adjustments for biosimilars, another discussion that gained quite a bit of traction in 2020 was around establishing a biosimilar shared savings model. Such a policy has been on the industry’s radar for years, especially following the U.K.’s gainsharing successes in 2017 and 2018. Establishing a shared savings program in the U.S. has sparked excitement amongst providers and biosimilar companies, as well as raised questions about how it could be successfully rolled out. Though this policy is under consideration via the Center for Medicare and Medicaid Innovation (CMMI), it’s important to note that the movement does not need to end there. In fact, these policies should be and already are being explored on smaller, regional scales between employers, sites of care, and payers.
Overall, such policies are clearly reflective of continuous learnings from Europe’s own biosimilar acceptance and uptake journey. The U.S. has heard for years about the success and overall market sustainability that can come from making sure all stakeholders’ needs are taken into account. As the U.S. sets its sights on prescribing practices, broader education, and value-based-care reimbursement, it’s clear we’re transitioning into a more nuanced and mature view of how to promote a more productive and sustainable biosimilar ecosystem overall.
The same argument can also be made about Europe, in part thanks to the publication of IQVIA’s Country Scorecards For Sustainability. These scorecards tabulate how well each European country is using biosimilars, which policy efforts are working, and which require more attention. The hope is that these will help EU countries prioritize specific strategies to implement biosimilars or improve their existing biosimilar utilization frameworks.
4.) Disparagement Under Fire: Creating An Equal Playing Field
Literally a week before the U.S. shut down, the biosimilar industry came together in-person one last time to attend a historical event: The FDA/FTC Workshop on a Competitive Marketplace for Biosimilars. Since beginning my tenure in the biosimilar space, I’ve called attention to a subtle shift in the FDA’s purview. Though the agency remains first and foremost a scientific organization, the biosimilar industry has introduced the FDA to challenges outside of the science After all, the agency is the gatekeeper to the market. A regulatory approval (patents aside…) can guarantee efficient market access, while scientifically accurate stakeholder education can improve confidence in biosimilars.
Since 2018, the FDA and FTC have embarked upon a critical partnership to ensure that biosimilars get a fair shake at the market. March 2020's workshop was a long-awaited event through which the industry could articulate its remaining needs/desired clarifications from the FDA, as well as discuss what biosimilar market “equilibrium” might (and currently doesn’t) look like.
Overall, 2020 was a big year for calling attention to the persistent challenges we face in creating an equal biologics playing field. In particular, there were a few events that suggest the FDA, FTC, and the industry are intent on banishing the frustrating fear-mongering tactics that have plagued biosimilars since day one. We saw our first official publication calling attention to the wide variety of misinformation we’ve seen throughout the years.
It was also reassuring to see that the FDA is quietly carrying out a study to determine the impact biosimilar disclosure statements might have should they be included in biosimilar promotional materials. This was arguably one of the least publicized events of the past year. However, it shows a firm understanding within the FDA of just how much words matter in creating that coveted equal and scientifically accurate playing field.
3.) The Biosimilar Regulatory Sphere Gets Even More Transparent
Along with healthcare workers, (the often severely understaffed) regulators have been unsung heroes of the year. Understandably, the agencies have had to redirect focus toward the much-needed COVID-19 vaccines and therapeutics. As such, it may have seemed on the surface like a slower year from a regulatory standpoint for biosimilars. But I’d argue 2020 contributed several critical milestones that will strengthen the greater push for a more sophisticated, streamlined, and harmonized biosimilar regulatory pathway.
The past few years have been characterized by evolving discussions around which types of data regulators still need — and which types are arguably less necessary. The FDA and EMA have both expressed their expectations of a future without large and expensive biosimilar comparative efficacy studies. However, many of these arguments have been limited to theoretical “yes we can” or “no we cannot” statements. It wasn’t until this year that we finally saw the “yes we can” argument spelled out concretely in the data in a high-profile IGBA BioDrugs publication.
It’s often argued that comparative efficacy trials aren’t sensitive enough to demonstrate how the subtle differences between a biosimilar and its reference product impact a biosimilar’s clinical profile. In his BioDrug’s paper, lead author Martin Schiestl did a deep dive into 13 years-worth of FDA and EMA biosimilar regulatory filings, arriving at this very conclusion: comparative efficacy studies did not uncover any new information about each approved biosimilar. These data go a long way toward providing regulators with a clear case as to why such large clinical studies do not need to be routinely prescribed for approval.
Of course, as Schiestl explained in this Biosimilar Development interview, not every biosimilar candidate will be suitable for a comparative efficacy trial waiver — a point that these clinical experts elaborated upon further in this article on clinical trials of biosimilars’ past, present, and future. Similarly, such regulatory evolutions will demand the best of companies in their analytical comparability, process validation, and good manufacturing practices — all of which were identified as common stumbling blocks in biosimilar regulatory filings in this 2020 study.
This information gathering over the past few years culminated in what was perhaps the largest regulatory news of the year for biosimilars: the publication of a position paper and draft guidance by regulators from the U.K.’s MHRA. In these documents, the regulators explain the limitations of comparative efficacy trials and establish a blueprint for regulatory submissions of biosimilars without such studies. The agency is feeling particularly ambitious; it hopes to turn this blueprint into reality starting in January 2021.
Outside of the often all-consuming “will they, won’t they streamline” debate, the WHO published results of a survey showcasing four regulatory challenges impacting biosimilars in 20 member countries. These issues include insufficient access to reference products, resource deficiencies, product quality challenges, and murky interchangeability and naming practices. To confront these issues, the WHO has put forth a list of strategies, many of which aim to increase collaboration across regulatory agencies and strengthen pharmacovigilance practices globally.
2.) The U.S. Finally Reaches The “Golden Age” Of Implementation
I’ve been waiting for five years to type the above sentence. Whether we’ve truly reached the “Golden Age” is still up for debate as there remains a lot of education, uptake, and policy work to be done. But multi-product biosimilar competition in oncology combined with heightened financial pressure from COVID-19 have created a perfect storm of biosimilar demand.
Over the past year, I’ve strived to provide insights from the different healthcare stakeholders and sites of care across the U.S. As this article demonstrates, nurses in the changing world of oncology have embraced the biosimilar opportunity wholeheartedly. We also cannot overlook hospital pharmacists; we have them to thank for getting biosimilars on hospital formularies and educating their healthcare systems on the importance of using these medications.
Integrated delivery networks (IDNs) like Kaiser Permanente have shown us a utopia in which biosimilar uptake can be seamlessly prioritized and productive from a cost-savings standpoint. But biosimilar usage is no longer limited to IDNs. As independent cancer centers explore the wide variety of CMS value-based reimbursement schemes, biosimilars are an increasingly important way for sites of care to reduce overall spend and meet CMS’ performance benchmarks. Hospitals may even be undergoing a future biosimilar growth spurt, despite the past few years of lagging behind other sites of care on biosimilar education and uptake. As one AmerisourceBergen expert explained, he’s been receiving an unprecedented number of calls from hospitals and health systems that, prior to the pandemic, had not yet embraced the biosimilar opportunity. Following months of quarantine, cash-strapped sites of care are getting more serious about benefiting from system-wide savings.
Education, education, education has been the industry’s endless mantra since day one. But 2020 was the year where the industry really started to feel as though these educational efforts and the mountains of global real-world evidence have started to make a difference. Though there will always be work to do to get stakeholders up to speed on biosimilars, we must not overlook the (very) comprehensive efforts healthcare providers have undertaken to implement biosimilars. 2020 should leave us in awe of our healthcare workers, not only for their tireless work through the pandemic but also for their leadership in spearheading the U.S.’ long-awaited biosimilar charge.
1.) The Biosimilar Industry Glimpses Future Opportunities And Faces It’s Biggest Question Yet
Over the next few years, biosimilar launches will be limited to the reference products that currently have one or several marketed biosimilar competitors (i.e., infliximab, filgrastim, rituximab, etc.) The next big “new” launches the U.S. can anticipate will be the army of Humira biosimilars waiting patiently for 2023. There is also the question of when the U.S. will get a much-needed Enbrel biosimilar after a disappointing court ruling that Amgen’s exclusivity could last until 2029.
In the meantime, the biosimilar business model will be facing a critical but challenging period of maturation. While all the biosimilars launching today are for reference products garnering several billions in sales per year, the future market opportunities are shifting. We see this shift clearly in an IQVIA report entitled “Biosimilars In The U.S.: 2020-2024.” As IQVIA reveals, there remains a vast amount of opportunity for companies willing to brave biosimilar development for what will be comparatively lower-revenue reference products.
There are currently 22 reference products with future-wave biosimilars in development. In total, this represents a 67 billion-dollar opportunity. But these 22 reference products only account for 50 percent of the biologics viable for future biosimilar competition. The other 50 percent comprises 153 molecules, or a 68 billion-dollar opportunity. Of these 153 molecules, there are 36 reference products facing patent expirations by 2025 that do not have any biosimilars in development. However, more than half of these 36 products (20) bring in less than $100 million in annual sales.
This leaves the biosimilar industry facing a critical question of identity. There will always be companies striving to develop biosimilars for more lucrative biologics. In fact, 14 of the 22 molecules with biosimilars currently in development bring in more than $1 billion a year (i.e., Xolair, Stelara, Keytruda, Eylea, and Lucentis). But the biosimilar industry has long prided itself on bringing affordable biologics to the patients who need them, and there are a lot of biologics and patients that could benefit from the presence of a single competitor. So, I pose the following question: can and will the industry truly live up to its purpose of greater access for the many biologic products as opposed to the financially alluring few?
Now I know what you’re thinking — investing in small-revenue products is hardly a question of willpower and desire as much as it is the question of whether these products are feasible from a COGs standpoint. This is why the preceding four developments discussed in this article are so crucial; they are the goalposts the industry should continue to evaluate and push for over the upcoming years. But it also comes down to you, dear readers. In addition to doing your part in advocating for these global measures of progress, there are also a number of considerations you can ask in your roles over the next few years to futureproof the biosimilar industry.
Be it a more cost-effective regulatory pathway, increasingly efficient analytical and manufacturing practices, more sustainable policies, or greater market uptake and confidence, these factors will pave the way to success of the future non-blockbuster biosimilar business model.
Honorable Mentions (in no particular order)
The U.S. Biologics Price Competition and Innovation Act (BPCIA) celebrated its 10th anniversary on March 23, 2020. This was also the date on which several products formerly regulated as drugs (e.g., insulins and growth hormones) were reclassified as biologics. Moving forward, these “transition products” will be approved as novel biologics or biosimilars.
In an effort to clarify its murky interchangeability designation, the FDA released a new guidance entitled Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act.
In December, AMCP held a multi-stakeholder partnership forum entitled “Biosimilars: Policy, Practice, and Post-Marketing Surveillance To Treatment and Coverage Decisions.” It resulted in a list of specific strategies to help the managed care space better navigate the arrival and growth of the biosimilar market.
Following the merger between Mylan and Pfizer’s former Upjohn business, the biosimilar division of Mylan has become part of the newly named business, Viatris.
After quite a long haul of speculating about the fate of the ACA and, in turn, the BPCIA, Supreme Court oral arguments in November have left many in the industry feeling optimistic about the longevity of the biosimilar legislation. We will find out the Supreme Court’s final ruling in spring 2021.
The success of the Australian Generic Biosimilar Medicines Association’s 2019 Biosimilars Week resulted in the IGBA celebration of Global Biosimilars Week from November 16-20th.
Boehringer Ingelheim submitted a Citizen’s Petition to the FDA asking the agency to reevaluate its current interpretation of the term “strength.”
The FDA launched its first iteration of the Purple Book, a searchable online database of licensed biological products. The long-term goal is to make the Purple Book highly similar (pun intended) to the Orange Book by including exclusivity information.
Biocon garnered a $150 million investment from Goldman Sachs.
Samsung Bioepis released long-awaited and much appreciated real-world data of Renflexis’ performance in IBD patients from the U.S. Veterans Affairs Healthcare System database. The results demonstrated success with a single switch from infliximab to Renflexis, as well as successful “double switches,” first from Remicade to Pfizer’s Inflectra, then from Inflectra to Renflexis.
A literature review of 178 biosimilar single switch studies in 21,000 patients reiterated what this 2018 literature review showcased: switching to a biosimilar does not result in major safety, efficacy, or immunogenicity issues.
Biosimilar companies including Amgen and Pfizer have been reporting some impressive growth in biosimilar sales, thanks to oncology biosimilar successes.
A study published in JAMA Internal Medicine suggests that biosimilar comparative efficacy studies can be longer, larger, and more costly than some pivotal trials for originator biologics.
Representative Glenn Grothman (WI) introduced the H.R.8190 Biosimilar Insulin Access Act of 2020. This bill would enable any insulin biosimilar approved by the FDA to also be automatically deemed interchangeable.
In recent weeks, the Trump Administration finalized two drug pricing policies: the controversial "most-favored-nations" rule and “the rebate rule.” Despite the fact these were finalized, there remains a healthy amount of skepticism that neither of these policies will actually be officially implemented.
Sandoz Canada and Samsung Bioepis both launched large-scale education campaigns in 2020 —Sandoz’s The Biosimilar Generation and Samsung Bioepis’ whitepaper entitled “Education In Biosimilars.”
Cardinal Health released a report showcasing rheumatologists’ current understanding and knowledge gaps on biosimilars.
The Midwest Business Group On Health and the National Alliance Of Healthcare Purchaser Coalitions both launched educational documents encouraging employers/employer coalitions to embrace biosimilars and engage in more informed health plan negotiations.
In March, the ERISA Industry Committee (ERIC) launched a large initiative entitled “Biosimilars: Employers And Employees See Savings, More Competition Needed” to present the current biosimilar opportunity to employers and provide strategies for greater employer adoption.
Several large U.S. employers have begun sharing their biosimilar implementation success stories.
A Tufts survey of the 17 top U.S. commercial payers revealed that a majority of payers were more inclined to prefer coverage of originator biologics as opposed to biosimilars. However, it’s also important to note that 53 percent of those surveyed covered biosimilars and their reference products at parity — a coverage option highly preferred by sites of care and manufacturers.
Canadian provinces continued to advance their wide-scale biosimilar transition programs. So far, British Columbia, Alberta, and Ontario have either launched transitions or announced their intentions to do so for infliximab, etanercept, and insulin glargine biosimilars. Halfway through the year, B.C. and Alberta announced the inclusion of rituximab biosimilars in their transition programs for several non-oncology indications.
Celltrion launched its subcutaneous infliximab, Remsima SC, in Europe in early 2020. The treatment received EMA approval for five additional indications in July 2020. Keeping the “bioinnovators” coming, the company has also signed on to collaborate with Intract Pharma on an oral version of infliximab.
The WHO prequalified Celltrion’s Truxima (rituximab) and Herzuma (trastuzumab). These two biosimilars join Samsung Bioepis’ Ontruzant (trastuzumab), which was the first prequalified biosimilar in 2019.