Replies to post #41491 on Biotech Values

[DewDiligence]

VRTX – Here’s the relevant passage from the
CC. I’ve highlighted the important stuff in
bold face. (CC transcript c/o ‘rolatzi’ on iV).

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Yaron Werber - Citigroup

…When you look at the end of treatment response and ultimately SVR, are you calculating that on an ITT versus based on or is this last observation carried forward? I'm trying to ascertain, what happens to the patient who drop out only the placebo 950 and continue in the background. How are they going to be calculated at the end?

John Alam

[This answer is textbook doubletalk, IMO.] So for the next analysis, our focus is on the relapse rate, which is the analysis of SVR 12 data of which is basically, have patient who stopped at 12 weeks or earlier in PROVE 1. stopped all treatment including interferon ribavirin and telaprevir. What the rate of relapse is out to 12 weeks of follow-up, and that is a very specific question again, we're asking to try to understand whether it's 12 weeks of, in fact, the interferon and ribavirin is sufficient or whether our focus should be on in that study and the PROVE program overall on the -- in particular the 24-week arm, which is 12 weeks of the three drugs with 12 weeks of follow back 12 weeks of pegylated interferon and ribavirin. And we're really looking at the -- you know it's dialing in or dialing up what the duration of the peg interferon and ribavirin would be. In terms of the final analysis, if your question is in PROVE 1, PROVE 2, PROVE 3, SVR rates when we put everyone together -- in the final analysis, which will be occurring much later in 2007 and in case of PROVE 3 into 2008, that will be absolutely an ITT analysis.

Yaron Werber - Citigroup

…just to clarify, let's say if your patient in arm 1 of the study and week six, you dropped out either with the placebo or 950, but you remain in the background regimen…and you showed-up for your blood test of 12 weeks. Is this patient at an ITT and what happens if they don't show up after 12 weeks? Do you take their last observation carry forward? I'm talking about the drop out within each arm before you get to the end of treatment.

John Alam

Yeah. I have to respect the other people that are on the line, with questions. Can we take this question offline? Joe could be available right after the call, and we would be happy to answer it. But given the detail of the question, let's move on to the next question out of respect to other people waiting.
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[DewDiligence]

VRTX – Here’s what Werber has to say about
the dropout-related statistics in his report that
just came out (bold-face emphasis is mine):

>>
The PROVE studies are designed to yield end-of-treatment and sustained viral response (SVR) data based on a true intent-to-treat (ITT) basis. That is, if a patient receiving VX-950 or placebo +/- PEG-IFN/ribavirin drops out of the trial, they are encouraged to have their blood drawn at 12 weeks and are included as part of the analysis.

This method can shift the data in either a positive or negative manner with respect to VX- 950. If a patient receives VX-950 for 2 weeks and is taken off of the drug due to tolerability issues, but remains on PEG-IFN/ribavirin for the remainder of the 12 week period and is found to be a responder, then that patient would be counted as a responder in the VX-950 group (despite having only received VX-950 for [only] two weeks). This would obviously benefit of Vertex.

Similarly, if a patient receives VX-950 for only a short period of time and fails what is mostly a PEG-IFN/ribavirin regimen, that patient would be counted as a VX-950 failure, to the detriment of Vertex.

It remains to be seen how the FDA will interpret this approach. It is possible that the FDA may prefer a stricter approach, whereby patients who dropout after receiving VX-950 or placebo are considered failures no matter what the outcome of the patient is at 12 weeks. This approach could skew the statistics of the trial against VX-950.
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