The arguments in favor of streamlining biosimilar development are many, and support for it is broad, including regulators, biosimilar makers (of course), scientists, and other stakeholders. We’ve published several posts since 2021 on the need to reduce or eliminate the reliance on comparative clinical trials for biosimilar approval. See the following for a sample:
- Streamlining Biosimilar Development
- Simplifying Biosimilar Development to Ensure Long-Term Competition
- Can Biosimilar Development Costs Be Genericized?
- Advancing Global Harmonization of Biosimilar Evaluations
- Biosimilar Opportunities and Barriers From the 2024 Festival of Biologics Meeting
Well, you get the idea. The reasons why streamlining biosimilar development is such a good idea at this juncture is not simply limited to lowering the cost of biosimilar R&D (the economic case); the scientific case is extremely strong. Furthermore, two of the expected implications of this economic benefit are to help address “the biosimilar void” (discussed below) and to significantly broaden patient access, the latter of which is a compelling argument from the societal perspective.
According to Gillian Woollett, DPhil, Head, Regulatory Strategy and Policy, Samsung Bioepis and Co-Chair, International Generic and Biosimilar Medicines Association Biosimilars Committee (IGBA), “Comparative clinical studies lack scientific validity and offer no new information to regulators or health care providers.” In an IGBA press release, she stated, “The savings in time and resources from eliminating these duplicative requirements could have a meaningful impact on patient access.”
The IGBA’s position papers on streamlining clinical trial requirements (April 2024) and supporting a global comparator for biosimilars (August 2023) clearly delineate the scientific and economic rationale behind these moves. These positions are not new. Indeed, Dr. Woollett has co-authored seminal papers on these topics with Dr. Christopher Webster in 2017, 2019, and 2021. Individually or combined, these regulatory changes would significantly affect the costs and time required for biosimilar development. Several statements by the FDA over the past 2 years indicate that the agency supports such a move.
Biosimilar Development Efficiencies and Patient Access
How do the economic implications of streamlining biosimilar development improve patient access? At present, biosimilar products are approved for 17 innovator biologics. Biologic licensing applications are being evaluated for a couple more (e.g., omalizumab, insulins aspart and lispro, and perhaps one or two other drugs that have not been publicly disclosed). However, dozens of biologic medications for which marketing exclusivity has expired (or is nearing expiration) have no pending biosimilar competition. IQVIA characterized this as a biosimilar void, which will only widen as an increasing number of biologics lose marketing exclusivity.
By changing the requirement on mandatory clinical trials, we would lower the cost of development and potentially shorten the time needed to obtain approval. These factors could influence a manufacturer to enter a less-lucrative market (e.g., < $1 billion in annual revenues), where most of these unchallenged biologics reside. IQVIA’s 2023 report referencing Europe’s biosimilar pipeline and void indicated that of biologics with less than €500 million annual sales forecast to lose marketing exclusivity through 2032, only 7% have prospective biosimilar candidates. And yet these lower-revenue biologics comprise three quarters of the total. The existence of a less-expensive biosimilar option could enable better patient access to several useful therapeutic biologic compounds.
Streamlining Biosimilar Development Should Support Biosimilar Competition
Experience has shown that rate of drug price declines is directly related to the number of products competing in the category. For products covered under the medical benefit, net drug prices had fallen about 15% per year for the first three years of biosimilar availability. For the adalimumab category, a pharmacy benefit–covered drug, prices have fallen as much as 85% below that of the reference agent’s wholesale acquisition cost. At some point, the drug prices will reach a floor and begin to rebound. In one drug category (pegfilgrastim), we’ve seen US average sales pricing actually bounce up significantly after reaching a floor.
However, in some cases, the manufacturer decides to withdraw existing biosimilars from the market. This could be exacerbated in Europe, where some countries utilized “winner-take-all” tenders. What happens if only one biosimilar drug is left in the category, where even the reference product has given up their marketing efforts?
A paper from a team headed by Marcin Stajszczyk, MD, PhD, Head of the Department of Rheumatology and Autoimmune Diseases, Department of Rheumatology and Autoimmune Diseases, Silesian Center for Rheumatology, Orthopedics and Rehabilitation, Ustroń, Poland, studied this phenomenon with etanercept.
Etanercept is not yet marketed as a biosimilar in the US because of patent issues. In Europe, biosimilars for this biologic have been available since 2017. The etanercept tender-contracting market has waned to the point that, ironically, only one biosimilar remains—meaning that the market is once again a monopoly, but not by the innovator product Enbrel® as in the years before 2017. Relative to the 5-year period after two biosimilars were launched (2017–2022), etanercept tender prices have increased nearly threefold. The most recent tender price, at €15.82 per “daily defined dose” is still roughly half the price of Enbrel before biosimilar competition was introduced, according to correspondence with Dr. Stajszczyk. However, are further price increases likely? Without additional competition, there is little to prevent it.
This Polish experience may portend future issues for biosimilar competition unless the evolutionary regulatory recommendations by many associations like the IGBA and industry experts like Dr. Woollett, are implemented and soon. The scientific, economic, biosimilar competition, and patient-access arguments are too strong not to finally take action to streamline biosimilar development.
(This post was updated on July 29 to reflect corrections to the spelling of Dr. Stajszczyk’s name).