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Will FDA’s approval of Semglee create a surge in the development of interchangeable biosimilars?
The holy grail for expanding access to less costly biotech therapies in the United States has been FDA approval of interchangeable biosimilars that do not require a physician to prescribe the alternative treatment. The development and utilization of biosimilars has been slow and disappointing since Congress enacted the Biologics Price Competition and Innovation Act (BPCIA) in 2010 authorizing follow-on products in this area. FDA has approved only 30 biosimilars since then, with just 20 on the market through 2020. But on July 28, 2021, FDA authorized the first interchangeable biosimilar for the US market, raising hopes for more affordable biotech treatments to come (1). It was no surprise that the first interchangeable is for an insulin therapy, predicted to reduce costs for some of the nation’s 34 million diabetics and setting the stage for what analysts expect to be a surge in the development of interchangeable products.
Despite FDA assurances that biosimilars are as safe and effective as innovator therapies, prescribers have been slow to switch patients to these alternatives, especially where brand manufacturers warn of adverse reactions to products undergoing an abbreviated testing process. Extensive patent protections and complex legal issues have enabled innovators to delay new competition, as has the need for a physician to prescribe the follow-on product.
Now all eyes are watching closely to see how well an interchangeable product competes with a well-established brand. FDA approved Semglee—made by Viatris and Biocon Biologics (formerly Mylan)—as interchangeable with Sanofi’s Lantus, a long-acting insulin analog. FDA Acting Commissioner Janet Woodcock praised the action as “momentous,” emphasizing the agency’s support for a competitive marketplace for biological products and for increasing patient access to “safe, effective, and high-quality medications at potentially lower cost” (1).
FDA also emphasized its rigorous testing and analytical process for documenting that a biosimilar has “no clinically meaningful differences” with its reference product and that there are no additional risks for a patient switching to an interchangeable treatment. The key to expeditiously developing less-costly biosimilars is the ability of manufacturers to conduct analytical studies to confirm the structural and functional similarity of a proposed biosimilar to a reference product. Biosimilar manufacturers do not need to conduct many expensive and lengthy clinical trials to establish similarity, FDA explains, but may rely more on extensive structural and functional comparisons (2). To document interchangeability, however, the manufacturer has to conduct switching studies to demonstrate that there are no added safety risks or decreased efficacy for an individual moving between the reference product and biosimilar (3).
At the same time, FDA and other regulatory authorities recognize that large-molecule biologics are not identical copies of a reference drug and usually contain a mix of many slight variations of a protein. Manufacturers thus need to submit data showing similar variations compared to the brand. Additional animal toxicology and clinical pharmacology studies support the structural and functional assessments, and manufacturers look to control for the pattern and degree of variations between different batches to ensure that safety and effectiveness does not change.
Despite years of disappointment, recent progress has fueled predictions for significant growth in biosimilars, even before FDA’s action on Semglee. A report from IQVIA issued in October 2020 predicted an accelerated increase in biosimilar approvals and sales that will yield $100 billion in savings over five years. As biotech therapies account for a larger portion of the prescription drug market, the analysts expect an increase in biosimilar development programs and greater uptake of these competitive products by prescribers and patients (4).
Similarly, a new analysis by Amgen on the current state of the US biosimilar marketplace predicts significant growth as more biosimilars launch at deep discounts and capture larger market share (5). In addition to financial savings, the analysts believe that payers and providers will support biosimilar uptake, as confidence grows in manufacturers’ ability to produce high-quality products and ensure reliable supply.
FDA also is assisting firms in navigating innovator patents and exclusivity periods with an update and expansion of its Purple Book of approved biological products. Budget legislation approved by Congress in December 2020 instructed FDA to include important patent and technical information on reference products to facilitate the development and approval process for biosimilars (6).
The legislators also are eyeing measures to deter innovator promotional messages that disparage follow-on competitors, spurred by FDA criticism of an Amgen promotional communication for undermining consumer confidence in biosimilars to its Neulasta (pegfilgrastim) injection. In July 2021, FDA’s Office of Prescription Drug Promotion (OPDP) sent Amgen an Untitled Letter criticizing the company for making a false claim of greater adverse events with the injection system used by biosimilars compared to the Amgen product (7). OPDP advised Amgen and other firms to “carefully evaluate the information presented in promotional materials for reference products or biosimilar products” to ensure correct product identification and avoid consumer confusion.
Additional action on Capitol Hill may advance biosimilar use, such as legislation approved earlier this year by the Senate that increases public access to information on biosimilar and interchangeable products to help address patient concerns. Even more important for biosimilar makers is to enact measures that enhance Medicare reimbursement for follow-on products by revising the payment formula for biosimilars under Part B and requiring favorable formulary placement by Part D drug plans.
1. FDA, “FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes,” Press Release, July 28, 2021.
2. FDA, Interchangeable Biologic Products, Fact Sheet, accessed Aug. 12, 2021.
3. FDA, Biosimilar Regulator Review and Approval, Fact Sheet, accessed Aug. 12, 2021.
4. IQVIA, Biosimilars in the United States 2020–2021, Competition, Savings and Sustainability, Institute Report, Sept. 29, 2020.
5. Amgen Biosimilars, 2021 Biosimilar Trends Report, Current State of the Marketplace, Amgen (2021).
6. FDA, “FDA In Brief: FDA Enhances Purple Book to Support Transparency in Biosimilars,” Press Release, Feb. 24, 2020.
7. FDA, Letter to David Shechter, PhD, Senior Manager, Regulatory Affairs, Amgen, July 7, 2021.
Jill Wechsler is BioPharm International's Washington editor.
Vol. 34, No. 9
When referring to this article, please cite it as J. Wechsler, “Biosimilars Move to Center Stage,” BioPharm International, 34 (9) 2021.