By Anna Rose Welch, Director, Cell & Gene Collaborative
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It’s hard to believe we find ourselves at the end of yet another year — and a difficult one to boot. Those of you who are regular readers of Biosimilar Development will note that there was absolutely no prediction amongst members of the editorial board in December 2019 that the industry (and all of us personally) would be faced with a global pandemic in 2020. But aside from the confusion, grief, exhaustion and “insert a million other feelings here,” 2020 was perhaps the most significant year yet for biosimilars globally, and especially in the U.S. As the amazing members of the Biosimilar Development Editorial Board emphasize here, there is a lot to be thankful for in the biosimilar world. From successful regulatory approvals and commercial launches, increasing market access, and greater healthcare savings, biosimilars are finally starting to demonstrate their societal benefits. But as many are also careful to point out, there is still work to be done, particularly in the realms of regulatory, federal/national, and payer policies to encourage use and cost savings. Check out the first of what will be a four-part series showcasing the editorial board’s thoughts on the past year and the year(s) ahead.
AR Welch: 2020 marked the 10th anniversary of the BPCIA in the U.S. In the past 10+ years of biosimilar use globally, what milestone in the regulatory space, government policy, OR the commercial market (or your area of focus) do you feel is most important to celebrate today, and why? What does this milestone tell us about the road ahead for biosimilars?
The BPCI Act has advanced competition among biologic and biosimilar manufacturers by providing robust models for manufacturing/approval processes, as well as the supply chain operation to expedite product access to market. The cost savings of 20 percent to 30 percent offered by biosimilars is vitally important during the ongoing COVID-19 pandemic, but also throughout our patients’ lives. We continue to see an increasingly large, aging population living with chronic diseases such as cancer where, in some cases, they are dependent on one or more biologic medications. As overall healthcare costs continue to rise and we see a continual increase in patient cost-sharing by employers and insurers, biosimilars offer a much-needed, clinically efficacious, affordable alternative to the originator product, resulting in decreased financial toxicity and increased access for our patients. — Kathy Oubre, MS, COO, Pontchartrain Cancer Center
2020 started out strong for the biosimilar market: six of the 18 biosimilars available launched this year. One of the most notable and recent milestones fell on September 3, 2020. This day marked the five-year anniversary of the launch of the first U.S. biosimilar, Sandoz’s Zarxio. After five years, the growth in the number of biosimilars that have been approved and that are being developed demonstrates the continued, stable investment in this product category. Also in 2020, we’ve seen a significant increase in competition, especially in the oncology space. There are now five biosimilars competing in the trastuzumab market, which is great progress.
This year, we saw the availability of biosimilars fuel an uptick in biosimilar market share. Since launching five years ago, Zarxio has captured more than 50% of market share in the Filgrastim market. By the end of their second year on the market, biosimilars in three key oncology therapeutic markets (i.e. bevacizumab, trastuzumab, and rituximab) are set to reach nearly 60% combined volume share. The rate at which biosimilars are now gaining market share is significantly higher and faster than that of previously launched biosimilars, indicating that more stakeholders are finally adopting these therapies.
While the commercial market was experiencing record-breaking growth, the U.S. also experienced notable movement in the regulatory space. Back in March, the FDA added about 90 additional molecules to the biosimilar category, including insulin, human growth hormone, and infertility products. The expansion of the product category to include insulins presents a major opportunity for biosimilars as it will likely pave the way for these therapies that will be covered under the pharmacy benefit and Medicare Part D in 2021 and beyond.
It’s hard to believe that a little over a year ago we were still having a conversation about whether or not we should throw in the towel on biosimilars. The increase in pipeline growth, competition, and market share coupled with substantial regulatory policies in favor of biosimilars make the case that these products are here to stay. This momentum is expected to continue and increase in 2021. — Sean McGowan, senior director, biosimilars, AmerisourceBergen
The UK’s MHRA achieved a significant regulatory milestone in October 2020; it released its updated guidance for biosimilar development requirements (to be implemented on January 1, 2021). Of particular significance were the updates to clinical trial guidelines. The MHRA stated, “In most cases, a comparative efficacy trial is not considered necessary,” while also specifying that “the clinical comparability exercise should always include a pivotal comparative PK trial, which may include the measurement of PD markers if available.” These refined development requirements are very important as they are the first major implementation of what has been shown through a recently growing body of evidence: confirmatory Phase 3 efficacy trials comparing biosimilar candidates with their reference products have limited utility in the overall demonstration of biosimilarity.1,2,3,4
For the road ahead, widespread adoption of the MHRA’s regulatory position, such as from the EMA and U.S. FDA, would effectively remove one of the largest barriers (in terms of time and cost) to biosimilar development. Wider regulatory agency adoption of such a position would allow for a more competitive environment in which a greater number of developers can bring affordable biosimilars to market. — Noelle Sunstrom, CEO, NeuClone
The biosimilars market is poised to grow rapidly in the near future as this year marks the 10th anniversary of the BPCIA in the U.S. While the U.S. healthcare market has been slow to adopt biosimilar products, we believe the new FDA initiatives could lead to increased biosimilar uptake and potentially realize the BPCIA’s ultimate goal of reducing the cost of biologic drugs.
Celltrion now has U.S. regulatory clearance for three of its biosimilars: Remsima (Inflectra, (infliximab-dyyb), Truxima (rituximab-abbs) and Herzuma (trastuzumab-pkrb), which marks an important milestone in the company’s journey. As the U.S. makes up more than 50 percent of the world’s total biologic drug revenues, we anticipate the FDA’s approval of our three main drug products to spearhead our sales in the U.S. market.
Although there are still some clearer regulations and policy measures to be put in place to drive biosimilar uptake in the U.S. — for example, pharmacist-initiated substitution (interchangeability in the U.S.) and anti-competitive contracting — we remain committed to continuously working with our stakeholders to overcome these challenges over the years to come. — HoUng Kim, head of the medical and marketing Division, Celltrion Healthcare
2020 marks the 10th anniversary of the enactment of the BPCIA and 5 years since the launch of the first biosimilar in the U.S. We continue to see the U.S. biosimilar market gradually evolve. The FDA has now approved 28 biosimilars and 18 biosimilars have launched in the U.S. market with varying degrees of market penetration. Yet, despite the increase in FDA approvals of biosimilar medicines, biosimilars have not reached their full potential in unlocking savings and expanding patient access due to remaining barriers. As we look forward to the next decade of biosimilars, industry stakeholders and policymakers must focus on the lifecycle of biosimilars post-FDA approval and identify opportunities to incentivize and expand utilization so that patients and payors receive the full benefit of lower-cost biosimilar medicines.
Expanding the biosimilars market is critical to achieve a more robust, diverse, competitive market that will provide more treatment options for patients and potentially help make these critical medicines more affordable. According to the IQVIA Institute for Human Data Science, the broader adoption of biosimilars could ultimately help to reduce drug costs in the U.S. by $100 billion over the next 5 years.5 In order to realize the potential savings promised by the U.S. biosimilar market, we must have a sense of urgency and prioritize efficient regulatory policies and payment incentives that push beyond the status quo to break down barriers to biosimilar adoption and ensure greater and wider spread utilization of biosimilar products versus the originator. — Tiffany Fletcher, head of global biosimilar policy & access, international affairs & global policy, Viatris
Rather than pointing to a single event, I’m most excited to see the growing volume of evidence for biosimilars as safe and effective treatment options. Over the years, clinical and real-world evidence has consistently shown that patients can effectively and safely switch from the reference biologic to a biosimilar. In a 2018 systematic review of 90 studies on switching from a reference medicine to a biosimilar, which included seven biosimilars across 14 disease states and 14,225 individuals, the majority of the publications did not report differences in immunogenicity, safety, or efficacy.6 Other reviews have reached similar conclusions.7
Overwhelmingly, these and similar studies have led to greater appreciation today of biosimilars as tools to support an overburdened health system. As a result, the future of biosimilars in the U.S. looks increasingly promising. — Brian Lehman, MBA, MHA, RPh., director, strategic alliances & patient advocacy, Sandoz
In the self-insured employer market, we've seen improvements in health plan coverage policies for biosimilars. More plans are preferring biosimilar(s) or placing them at parity with a reference product (one notable exception is Remicade). That’s the good news, and it has been an evolution. The not-as-good news is a tendency to prefer ONE (1) biosimilar, causing havoc for practices’ inventory control and management. Moreover, competition is great, but if competitors must raise list prices to accommodate large rebates paid for formulary placement, we’re not achieving the full advantage that competition could offer. — Lauren Vela, Senior Director, Pacific Business Group On Health
The advent of multisource biosimilars has been a welcome sight in the employer benefits community. When only one biosimilar is available to compete with the reference product, the slight financial differences between the two have generally allowed the originator to control formulary preference in favor of “lower” net cost after rebates. That argument gets much tougher to make when multiple biosimilars are launched and price erosion ensues, which is what we are witnessing with infliximab, pegfilgrastim, and trastuzumab. The utilization management tools we use to promote multisource generics on the traditional drug side, such as step therapy and originator exclusions, will be effective strategies to push market share further to biosimilars. Employers struggling with specialty spend are eager to use them, so I am confident in the road ahead as more biosimilars are projected to launch. — Matthew Harman, PharmD, MPH, director of pharmacy, Employers Health
In 2020 in the EU, we are celebrating two key milestones: the biosimilar pathway was born 15 years ago in the EU and, astoundingly, we have reached more than 2 billion cumulative patient treatment days of safe biosimilar medicines experience. The value for patients and healthcare systems continues to grow every day, significantly contributing to reducing access inequities and creating earlier, broader, and future access opportunities through re-investment in better care. While these achievements are worth acknowledging, the Covid19 pandemic has highlighted that grave health inequities remain and more can certainly be done! — Julie Maréchal-Jamil, director, biosimilars policy & science, Medicines for Europe
I think we witnessed a big milestone when Zarxio (filgrastim-sndz) overtook its reference medicine to become the leading filgrastim option on the market.
To date, the success of biosimilars in the U.S. has been mixed. A few biosimilars have led to substantial cost savings, but others have not. Zarxio, however, stands out as a strong success story: the availability of biosimilar filgrastim generated approximately $1.2 billion in savings to the U.S. healthcare system from 2016 to Q1 2020, with Zarxio driving the majority of the market.
As more biosimilars receive FDA approval and become available to patients, we are beginning to see a greater understanding and appreciation for these medicines as lower-cost, effective treatments that can help address rising costs within the U.S. healthcare system. I think Zarxio’s market success has laid the groundwork for what will be a strong future for U.S. biosimilars.— Hillel Cohen, executive director, scientific affairs, Sandoz
I’ll happily celebrate the anniversary of the BPCIA, as the possibility the SCOTUS would find severability of ACA components appears more likely. We’ll not know the final result until around June of 2021, but some on SCOTUS have signaled their willingness to consider severability. Unfortunately, others there may have painted themselves into a corner with statements about their negative general views of severability when considering the constitutionality of controversial laws. Let’s hope the BPCIA “baby” doesn’t get tossed out with the “bath water” should other ACA components be deemed unconstitutional. — Ross Day, consulting hospital pharmacist, former director of pharmacy, Vizient
Canada has seen a fair bit of success in the last five years in terms of adoption and acceptance of biosimilars as a treatment option. From a policy perspective, there is now uniform support for biosimilars as a first option for bio-naïve patients. Acceptance of biosimilar transitioning/switching is growing quickly with provincial governments mandating these approaches and private payers increasingly following suit. All of these efforts are creating a strong market for biosimilars in Canada, and I expect these developments to continue to intensify going forward. Of all the developments that have occurred, the most material impact came from the provincial governments and their strong resolve in implementing policies that demonstrate their commitment to a viable biosimilar market. — Ned Pojskic, leader, pharmacy & health provider relations, Green Shield Canada
From a regulatory standpoint, the recent development of sophisticated analytical methods has helped assess biosimilarity to the point that (some) regulators no longer request Phase 3 patient trials. We’re also seeing (very) limited toxicological studies being requested by regulators — if at all. These data are occasionally still being requested officially in certain countries (e.g., Brazil). Overall, the FDA has been very supportive in facilitating the biosimilar approval process over the past two years.
On the commercial side, the COVID-19 crisis has, obviously, impacted all drug developments, including biosimilars. But we are still seeing stiff competition, which is reflected in the major discounts in the reference products price (up to 86 percent). Unfortunately, though, such steep discounts have led some to question the financial viability of the biosimilar market. — Francois-Xavier Frapaise, M.D., ClinExcel
There are many things to celebrate but they all come together in the successful launches and uptake of biosimilars. There have been some challenging launches in the past — in particular, that of infliximab — but recent launches have also done quite well, one case being rituximab.
To successfully develop and launch a biosimilar in a timely manner, so many things have to come together just right. In the past it was about the development, clinical development, and regulatory approval. We succeeded in that regard greatly. Next came the battle against misinformation, allowing physicians and patients to recognize and appreciate the benefit biosimilars bring to the market and to understand that they are safe and clinically equivalent to the reference product. The recent successes of biosimilar launches are a testament that our education and communication strategies have worked and that the real-world data, both in the U.S. and the EU, are becoming more and more convincing about just how effective and vital biosimilars are. — Edric Engert, managing director, Abraxeolus Consulting
I think the most important milestone to celebrate is the progress at the FDA in biosimilar approvals and development programs. To date, the FDA has approved 28 biosimilars since 2015 and has about 90 biosimilar development projects for 35 reference products. This is great progress for patients, providers, and payers in developing competition and advancing lower healthcare costs, but it is not enough after 10 years.
Although the progress at the FDA is commendable, there is a second chapter to the biosimilars story that is happening in today’s U.S. marketplace. Today, IQVIA reports that biosimilars have only a 20 percent market efficiency in the U.S., which indicates low uptake and even lower realized cost savings for consumers.
We need to look to the future. In 2021, stakeholders need to remove the barriers to access for biosimilars in the U.S., especially in our current COVID economic environment. Patients, families, and governments need real healthcare cost savings and biosimilars are a ready solution, waiting in the wings to do just that: create healthcare savings. — Julie Reed, VP, corporate affairs lead — I&I and biosimilars, Pfizer
In the Federal Circuit’s decision in Amgen v. Sandoz, the court analogized the BPCIA to Winston Churchill’s famous description of Russia as “a riddle wrapped in a mystery inside an enigma.” The court said it would “do [its] best to unravel the riddle, solve the mystery, and comprehend the enigma.” On appeal in that case, the Supreme Court issued its landmark decision finding that a biosimilar’s notice of commercial marketing can be given at any time, including pre-approval, and that the only remedy for a biosimilar applicant’s failure to engage in the patent dance is an immediate infringement suit by the reference product sponsor. This latter ruling has led to the common understanding that the patent dance is, in effect, optional. Since that important decision, more questions about the statute have been answered, but many remain unresolved. One issue that remains hotly contested is how much information a biosimilar applicant must disclose at the beginning of the patent dance, which hinges on the interpretation of the portion of the statute requiring an applicant to disclose its abbreviated biologics license application “and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application.” This and other questions will continue to be litigated for years to come. — Alexandra Valenti, partner, Goodwin Proctor
We now know that biosimilars can be approved based on a different data set that is customary for originator biologics, and that when they are used they behave exactly as expected and indistinguishably from their originator reference products. That is the good news.
The challenge is that we are overbuilding dossiers with data that is not actionable. So the process as a whole, both for biosimilar sponsors and for the regulatory Agencies, can hardly be considered abbreviated. It is different yes, but not efficient.
We need to use our experience to date to become way more focused and efficient in our development of biosimilars. This will save time as well as money so hopefully biosimilars will no longer have to cost 100 times that of the average generic to get through the approval process. After all, any unnecessary study is still one that the patients will have to wait for to be completed and ultimately, also, for which they'll have to pay. The same arguments apply to originator products too – science is remarkably fair! —Gillian Woollett, SVP, Avalere Health
- Frapaise, F., 2018. The End of Phase 3 Clinical Trials in Biosimilars Development?. BioDrugs, 32(4), pp.319-324.
- Webster, C., Wong, A. and Woollett, G., 2019. An Efficient Development Paradigm for Biosimilars. BioDrugs, 33(6), pp.603-611.
- Bielsky, M., Cook, A., Wallington, A., Exley, A., Kauser, S., Hay, J., Both, L. and Brown, D., 2020. Streamlined approval of biosimilars: moving on from the confirmatory efficacy trial. Drug Discovery Today, 25(11), pp.1910-1918.
- Schiestl, M., Ranganna, G., Watson, K., Jung, B., Roth, K., Capsius, B., Trieb, M., Bias, P. and Maréchal-Jamil, J., 2020. The Path Towards a Tailored Clinical Biosimilar Development. BioDrugs, 34(3), pp.297-306.
- Aitken M, Kleinrock M, Muñoz E. Biosimilars in the United States 2020-2024: competition, savings, and sustainability. IQVIA. September 29, 2020. Accessed October 6, 2020. iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024.
- Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. Drugs. 2018; 78(4):463-478.
- Barbier L, Ebbers HC, Declerck P, et al. The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review. Clinical Pharmacology & Therapeutics. (2020). https://doi.org/10.1002/cpt.1836.