FDA’s First Interchangeable Biosimilar: Floodgate for Others?
(Thursday, July 29, 2021)
Yesterday’s approval of the first interchangeable biosimilar by the FDA provides a proof of the concept for biosimilars that will be treated like generic drugs in that they can be substituted for the reference product at the pharmacy without needing a specific prescription. This is a major milestone that has been almost 10 years in the making since the enactment of the biosimilar regulations in 2012. FDA does not like to use the word “biogeneric” to describe interchangeable biosimilars but that’s perhaps the word for the layman to understand these products. Like generic drugs, the interchangeable biosimilars must be identical in structure and functions to the reference product and show comparability via switching studies that look a lot like BA/BE studies done for generic drugs. But that’s an over-simplification of the process to create interchangeable biosimilars. And the first approval is a good case to highlight the challenges that will be faced by other biosimilar developers with similar intent. Insulin is one of the most well-understood simpler protein; practically all aspects of the molecule have been studied over decades. Still the developer (Mylan Pharmaceuticals) conducted four large clinical trials to demonstrate that the biosimilar is almost identical to the reference drug in terms of safety and effectiveness and non-inferiority compared to the reference product. FDA published a guidance two years ago describing its expectations from the non-inferiority studies, also called “switching studies” where the biosimilar must demonstrate that it produces the same clinical result as the reference drug in patients and that the risks in terms of safety or diminished efficacy of switching between the biosimilar and the reference drug is not greater than the risk of using the reference drug without such switching. This guidance was written during the time Mylan was actively working on the analysis of its non-inferiority studies and likely was having intense discussions with the FDA for the design of those studies. That may have contributed, at least in part to the suggestions made by FDA in that guidance document. Such comparability would be harder to show for complex biologics with unique structural characteristics, acting on multiple targets or less-defined biological pathways. Interchangeability of the biosimilars is the holy grail for developers and although now we know it is achievable, it is not an easy path. Don’t expect too many biosimilars becoming interchangeable in the near future; we will see a trickle of these in the coming years not a deluge.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC