Extrapolation of Indications in Biosimilars

Bruce A. Feinberg, DO: There’s more complexity here, because of the chronicity of therapy with your patients. You’ve got this bouncing back and forth between agents, based on contracting with the payer. You’re going to introduce a biosimilar, so the argument in favor would be that it’s the same mechanism of action. But, it may be for an indication that wasn’t studied, so we don’t have any real direct evidence. It’s all indirect evidence. We may not have any familiarity.

So, you have a physician who’s being put in a situation where not only have they not used this drug, or have used this drug minimally, but they are also using this drug in an indication that has not been formally studied. You get layers of potential barriers. If you look at them from this standpoint, what’s the hardest hurdle to overcome? What’s the easiest hurdle to overcome?

Marcus H. Snow, MD: I can speak out of both sides of my mouth on extrapolation, because, as a rheumatologist, I treat conditions that are rare, unusual. I have a scleroderma clinic where I’m using medications that are not FDA approved for scleroderma.

Bruce A. Feinberg, DO: Marcus, you do know you’re saying this on camera?

Hope S. Rugo, MD: We all do that.

Marcus H. Snow, MD: There are no studies in this so, a lot of times, we have to work at this. The insurance company will call us back and say, “That’s not approved.” Then, we provide some data, some case reports. There are ways that we do this. But, as rheumatologists, big studies for us involve 200, 300 patients. In the cardiovascular world, that’s nothing. I do extrapolation. We use extrapolation all the time.

Bruce A. Feinberg, DO: So, you can’t use it by cherry-picking? That means that you’re saying, “It’s OK there,” but now I’m going to say, “No, it’s not OK here.”

Marcus H. Snow, MD: I think we have to use caution. An interesting exercise is that, with the infliximab biosimilar when it was approved in Canada, ulcerative colitis was withheld as an indication because it wasn’t felt that there was enough data because the mechanism of action in ulcerative colitis is different than rheumatoid arthritis. Subsequently, it did get approved. But, I think extrapolation by the FDA is allowed as long as it is—I have to get the wording exact—“deemed appropriate.” There’s some vague wording but, basically, it is allowed if it seems to make sense. And so, we’re going to see that, but I think this is where it falls back to the point that we need to have pharmacovigilance. If you start seeing things that aren’t working right—maybe this biosimilar is not doing as good a job for psoriatic arthritis as it does for rheumatoid arthritis—then those issues need to be addressed. But, extrapolation is tough, because it’s going to be necessary. For the companies that make these medications, it would be cost prohibitive for them to redo all the studies in all the indications.