The Extrapolation of Indications

Gillian Woollett, MA, DPhil: So, I’m going to move to the next issue, which is extrapolation, which is another much misunderstood issue. So by way of introduction, extrapolation is the use of a product for more than 1 indication, but for a biosimilar, when the studies are limited to other than complete clinical studies in every indication. Now, it’s the same as comparability, where if you make the same molecule, ultimately, it has to do the same thing clinically in all of the indications.

So I think what’s confused this debate a lot is that people are assuming it’s extrapolation between indications that may be fundamentally different diseases. So I just want to clarify that it’s not. It’s the same molecule, and it has to do the same thing as the reference did, as the premanufacturing change did. But it does mean we have more limited clinical data sets specific to the biosimilar on the day the biosimilar is launched.

Physicians are used to seeing clinical studies on each indication at the day of approval and launch of an originator product. So maybe to our physician, how much is this misunderstanding, based on the molecular match being the basis of extrapolation—how much is that confounding biosimilar uptake if there are no specific clinical studies on the biosimilar available to put in front of the physician?

Kashyap Patel, MD: So, I want to answer that question in a couple of different ways. First of all, extrapolation is something that’s very important—that the FDA kind of grants its designation to a drug when it’s approved, and maybe the FDA can play an important role in helping physicians understand what extrapolation is. And the second thing is, in oncology, if you trace back the history of how we use drugs, a lot of times we may not have phase 3 randomized controlled studies in all of the indications that we use. We initially, before [the National Comprehensive Cancer Network, NCCN] came into existence, used to use compendia listing for indications that were not part of the FDA-approved indication.

Subsequently, with NCCN establishing a robust pipeline evaluating, analyzing, and granting these data—like, you know 1A, 1B, or 2A—we are very comfortable that even if the drug has not undergone all clinical trials in all indications, if it comes into the guidelines, whether they’re the [American Society of Clinical Oncology, ASCO], [American Society of Hematology, ASH], or NCCN up to 2A, we would be very comfortable using that drug in those categories. Now, what the FDA could do is to help physicians understand about how extrapolation is kind of derived, and how it probably would be helpful.

Also, getting into the NCCN, or ASCO, or other guidelines would help a product get appropriate payer coverage, because we just don’t need to kind of look at the approval process; we also want to look at are payers and whether we cover that or not.

So, I think extrapolation is a very important part of the educational piece that does to be highlighted, and the FDA would be the most competent authority to do that in conjunction with not-for-profit educational forums.