- Dr. Fiona Greer, Independent Consultant
July 28th 2021 marked a milestone in biosimilar development. The US FDA approved the country’s first interchangeable biosimilar product-a once daily treatment for diabetes, marketed as “Semglee®”. In the US, the term “interchangeable” means that the marketed product can be substituted automatically by pharmacists without permission from a clinical prescriber, and so similar to the situation with generic drugs. Products that are approved as “normal”, rather than interchangeable, biosimilars are not permitted to be substituted.
Semglee® (insulin glargine-yfgn), manufactured by Biocon Biologics and distributed by Mylan (Viatris), has been approved by the FDA to be both biosimilar to and interchangeable with its reference product, Lantus (insulin glargine), manufactured by Sanofi. Insulin glargine is a long-acting human insulin analog prescribed to enhance glycemic control in both adults and children with Type 1 diabetes and adults with Type 2.
Semglee had already gained approval back in 2020 and has been commercially available since then. This news is the granting of a separate approval of interchangeable biosimilar status, sought to improve the product’s marketability. As this is the first interchangeable insulin biosimilar to Lantus, FDA approval grants it 12 months exclusivity before another interchangeable biosimilar to Lantus can be approved.
The US has been late entering the biosimilars arena, with the introduction of the Biologics Price Competition and Innovation (BPCI) act not until 2009 (five years after the EU guidelines), and has been struggling to catch-up since then. Unlike Europe, and in particular some Scandinavian countries, adoption in the US has been slow due to a myriad of issues including intellectual property challenges, pricing and contracting, payer controls and crucially, lack of awareness and/or acceptance of the concept by both patients and physicians.
The 351(k) pathway of the Public Health Services Act grants access to an accelerated licensing pathway based on comparison with a reference product already approved via the standard 351(a) route. However, in a concept unique to the US, the Act defines two types of biosimilar: a biosimilar and an interchangeable biosimilar. The definition of the latter is that the interchangeable product may be substituted by a pharmacist without the intervention of the prescriber. For approval, additional clinical studies are required to demonstrate that the same clinical result as the reference product can be produced in any given patient and that risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar and the reference product is no greater than using the reference product itself. The interchangeable designation doesn’t mean that the product is superior to a normal biosimilar, it demonstrates that the specific “switching studies” have been performed to provide evidence that there are no higher rates of problems or adverse events or decreased efficacy.
To date, a significant barrier to biosimilar uptake is both patient and physician lack of understanding and comfort with the concept of biosimilarity, particularly the option of switching treatments for patients who already well-tolerate the reference drug product. In many cases, lack of reliable information hinders the decision-making process. Although the FDA has published extensive educational guides for both patients and healthcare providers on its website(1), a recent action by the US Congress aims to promote education on biosimilars in an effort to encourage their uptake more widely. The Advancing Education on Biosimilars Act 2021, signed by President Biden on April 23rd 2021 mandates education on biosimilars for healthcare providers and designates the responsibility for this to the Head of the US Department of Health and Human Services, which oversees the FDA.
A 2020 National Diabetes Statistics Report compiled by the CDC (Centers for Disease Control and Prevention) estimates the burden of diabetes in the US, with around 34 million people (10.5% of US population) currently diagnosed with the disease and 88 million over 18’s with pre-diabetes ( 34.5%). Approximately a third of diabetes sufferers require treatment with insulin. The spiraling costs of drugs to treat and alleviate this disease have attracted Congressional interest for years.
Many new rapid and longer acting varieties of insulin have been developed by traditional insulin manufacturers. In addition, there are already a couple of “follow-on” insulins on the market which were approved prior to 2020 when insulin was transitioned to the list of biologics covered by the BPCI act. Basaglar in 2015 (insulin glargine, Lilly) and Admelog in 2017 (insulin-lispro, Sanofi ) were approved through the 505(b)2 pathway of the Food Drug and Cosmetic act. Semglee itself was initially approved in June 2020 under this route too. The announcement of the approval last week of interchangeable biosimilar status for Semglee will no doubt promote discussion in relevant medical and patient forums and highlight the issue of biosimilar insulins once again.
With insulins now being regulated in the US in the same way as all other biologic drugs under the PHS Act, and the 351(k) pathway being available for biosimilar versions, it is hoped that this will lead to greater competition among insulin manufacturers.
In a market characterized by high prices, time will tell if the introduction of interchangeable biosimilar insulins will bring more competition and lower the cost of these drugs. What is certain is that access to better and more accurate information regarding the process of developing, testing, and regulating biosimilars will lead to more understanding, acceptance and trust in treatments in the future.
(1) https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars
