Biotech Values

[mcbio]

JNJ Starts Phase-3 Trials of TMC435 in 1st/2nd-Line HCV

[TMC435 is a second-generation protease inhibitor that JNJ licensed from Medivir. All three of the phase-3 trials test SoC±TMC435 in genotyope-1 patients and use a 24w/48w “response–guided” protocol for determining when to stop treatment. The QUEST-1 and QUEST-2 trials in first-line HCV are clones; the only difference is that QUEST-1 uses Pegasys while QUEST-2 uses a choice of Pegasys or PegIntron. The PROMISE trial is in second-line HCV and is specifically for first–line relapsers (i.e. it excludes the harder-to-treat patients who never achieved undetectable virus in the in the first line). PROMISE is not being characterized as registrational, so the FDA has presumably not agreed that it alone is sufficient for approval in the second-line setting.

In phase-2b, JNJ/Medivir have reported 24-week data but not 48-week or SVR data (#msg-52204240); however, the companies presumably like the phase-2b data that have not yet been publicly disclosed.]

I have to say that I now feel better about ACHN's ACH-1625 vis-a-vis TMC435 now that I understand that 1625 is active against the same HCV genotypes as TMC435. 1625 is clearly behind TMC435 in the clinic with the key longer-term safety hurdles upcoming, but at least 1625 is active against the same HCV genotypes. I also like the fact that ACH-2684, due to enter the clinic shortly, is apparently the only other PI either in the clinic or about to enter the clinic, other than the MRK PI in Phase 1, that's active against HCV genotype 3. Genotype 3, although it's a small subset of U.S. HCV patients, is much larger outside the U.S. and is apparently one of the fastest growing HCV genotype populations. It still likely represents a nice market opportunity in just the U.S. market given the number of patients we're talking about, especially if we take this in the context of how small ACHN is and the impact that size market could have for ACHN. I guess the one important point to consider is whether or not NS5A inhibitors are ultimately going to supplant, or be used in conjunction with, HCV PIs. Since I believe they are pan-genotypic, this is presumably a concern to consider for any company focused exclusively on HCV PIs (ACHN of course has its own NS5A inhibitor about to enter the clinic).