Replies to post #106944 on Biotech Values

[mcbio]

Re: AZN Phase 3 FosD trials

The population AZN is studying is a tougher one than the broader RA population, and so proving efficacy against a placebo will actually be harder than it would be in the general RA population. But these days the FDA is all about risk vs benefit, and so the safety bar is implicitly lower for patients with an unmet need. Their drug is not quite clean (the hypertension issue) and so they have elected to go for the tougher population with an unmet need.

Thanks Peter. Actually, now that I think about it, it's this same type of patient population (anti-TNF failures) wherein RIGL saw FosD flop in Phase 2 (believe it was the TASKi3 trial). So, this type of design definitely carries more risk with it from an efficacy standpoint. There was some discussion that the TASKi3 failure may have partly been due to study design, so perhaps AZN has found a way to better tweak the design for this type of patient population.

I hear you on the unmet need point. The hypertension issue has been noted as one issue with FosD, but it only occurs in a small minority of patients and it seems like it has been quite manageable to date. Whether something worse crops up in Phase 3 or if the FDA will otherwise be a stickler if the same magnitude of issue crops up in Phase 3 remains to be seen.

All told, I have to imagine that AZN expects a large market for FosD in the marketplace (presumably a market well beyond just methotrexate and anti-TNF failures so I'm assuming they expect a bunch of off-label use in more front-line patients) given that they've indicated that this program is one of their top Phase 3 priorities.