FOR CHAR

Telaprevir and Peginterferon alfa-2a Therapy
Nezam H. Afdhal, MD, FRCPI:
There was a number of presentations on novel targets for the treatment of hepatitis C virus (HCV) in Boston this year. Before we consider individual studies, a couple of general themes are worth highlighting. First, the issue of resistance arising from the use of small molecule therapies is an important concept that was widely discussed. As resistance data are gathered, it appears likely that for the near future, most of the small molecule inhibitors, such as telaprevir (VX-950), R1626, HCV-796, and valopicitabine (NM283), will be used in combination with peginterferon alfa with or without ribavirin. The second overall issue discussed in this area was the importance of differentiating patients who have a greater or lesser chance of sustained response to these new therapies due to their likelihood of response to peginterferon-based therapies. Patients who are less likely to respond to peginterferon might in effect be receiving small‑molecule monotherapy, despite the coadministration of peginterferon. This issue was an overarching theme for this conference and will need to be addressed further by clinical investigators.

Turning to the specific studies, interesting data were presented on the use of the HCV protease inhibitor telaprevir. In particular, 3 studies examined the outcomes of HCV patients following therapy with telaprevir combined with peginterferon with or without ribavirin.[1-3]

In a subanalysis of the VX04-950-103 study, Kieffer and colleagues[1] reported on 8 HCV genotype 1 patients who received telaprevir monotherapy (750 mg 3 times daily) and 8 patients who received the same dose of telaprevir combined with peginterferon alfa-2a (180

[domusic]

Looks very interesting, and promising (I think). A little difficult to comprehend. Looks like they're beginning to understand why this "C" virus remains illusive to INF/Riba treatment in many HCV patients. I've been following the VX950 trials and am hoping at some point they can fast track the FDA approval. There is an urgent need to get this to market as long as it remains viable and safe. Perhaps we should petition the FDA.

DoMusic

[mremeet]

Thanks for the info pam, good stuff. I just wonder when they're finally going to address the subject of combining two or more protease (or polymerase) inhibitors for the purpose of treating HCV. I guess it's a little early for that, as all the PI's are still under development. But there's an urgent need for many who are either intolerant to IFN (due to AI issues etc) and/or ribavirin, or are simply unresponsive to it (antivirally speaking). And I don't see why they can't even start discussing the possibility/feasibility of a PI cocktail, using multiple (differing) methods to simultaneously put pressure on the virus, and hopefully elude the rise of PI resistant strains alluded to in this reference. Like combining Schering Plough's SCH503034 along with Vertex's VX-950. For the very first time, that might just do the trick without IFN/riba.

Hopefully they'll start talking along these lines pretty soon. It would be great to see a trial like this within a year or so. Both VX950 and SCH503024 appear to be coming along fairly well, and might just make for the dynamic duo many have been waiting for.

[Imagine]

I had to read it a couple of times, actually I may have already read it and forgot (may require a couple more times :)

Good Stuff!