Replies to post #74363 on Biotech Values

[microcapfun]

>>I’ll have to eat my hat because I was under the impression that the phase-3 Albuferon trials had SPA’s that specified non-inferiority to Pegasys as the primary goal and specified a (two-sided) non-inferiority delta of 12%, which was met in both trials.<<

I was surprised about that too, but here's the evidence:

7/30/08, 2Q08 cc ...

Joseph Schwartz - Leerink Swann

Yes, I think that is helpful. And then if I could follow-up on Albuferon as well. In terms of the non-inferiority bands that you have chosen, how confident are you that the FDA is on board with the comparisons that you have proposed and the magnitude of effect that will be considered, statistically, non-inferiority just given their problems with non-inferiority trials recently?

Davis Stump

We have clear end-of-Phase II agreement. This was a point of very specific discussion in our end-of-Phase II discussion with FDA where we set the boundary to be excluded of 12%. That roughly would translate in to the statistical outcome being met if Albuferon was no more than 5% worse – observed worse than Pegasys.

Non-inferiority trial design – that’s a whole day's conversation. You do better in non-inferiority trials when you have got more external data to point to. We were fortunate that we had the data comparing native interferon to placebo then having comparison between Pegasys to native interferon. So there is fair amount of data that pointed as a 12% margin is being clinically meaningful.

I am going to say that I do not think that was a great point of contention during the discussion. So I am pretty comfortable, short of us actually going and getting an SPA which we chose not to do because of the time that that would have taken, that we have agreement on that boundary.<<

I don't know very much about the inner workings of the FDA, but my impression is that an "end of Phase II agreement", if there is such a thing, is little more than non-binding FDA guidance and advice. Would there even be a document signed by the FDA which states something about the 12% margin? I doubt it.

micro