Replies to post #100306 on Biotech Values

[hptaxis]

Michelle M-P, Christiane S, Sarah M, et al. Twelve weeks post treatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology 2010;51(4):1122-6.
http://www3.interscience.wiley.com/cgi-bin/fulltext/123191081/PDFSTART

A sustained virologic response (SVR) in patients with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin is defined as undetectable serum HCV-RNA at 24 weeks (W+24) posttreatment follow-up. Viral load outcome in patients with virological relapse (VR) has not been explored. This study evaluated whether the assessment of serum HCV-RNA 12 weeks (W+12) after the end of treatment was as relevant as W+24 to evaluate SVR in 573 patients who received combination PEG-IFN and ribavirin and had a virological response at the end of treatment. Serum HCV-RNA was measured, using a new assay based on transcription-mediated amplification (TMA) with a lowest detection limit of 5-10 IU/mL, at W+12 and W+24 after the end of treatment. VR was defined as reappearance of detectable HCV-RNA at W+24 posttreatment follow-up. The positive predictive value (PPV) of undetectable serum HCV-RNA at W+12 was evaluated to identify patients with SVR, and the viral load outcome was measured in relapse patients. At the W+24 post treatment follow-up, 408 (71%) patients had an SVR, 181 (71.2%) were treated with PEG-IFNalpha-2a and ribavirin, and 227 (71.1%) were treated with PEG-IFNalpha-2b and ribavirin. At W+12, serum HCV-RNA was undetectable in 409 patients, and 408 patients were SVR (PPV 99.7%, 95% confidence interval 99.1-100). In relapse patients, serum HCV-RNA levels were 5.623 ± 0.748, 4.979 ± 0.870, and 5.216 ± 0.758 log10 IU/mL at baseline, W+12, and W+24, respectively.

Conclusion: Our results show that the assessment of serum HCV-RNA 12 weeks after the end of treatment, using the highly sensitive TMA assay (PPV 99.7%), is as relevant as after 24 weeks to predict SVR and make decisions on the management of treated patients, suggesting a new definition for SVR. (HEPATOLOGY 2010.)

[mcbio]

Re: HCV SVR12 vs. SVR24

Sooo, the relapse kinetics of ifn monotherapy and ifn+rib may not be that different. But/thus SVR12 might actually be a very good proxy for SVR24.

So, should I infer that you believe that SVR12 may be a good proxy for SVR24 as well where a combo of HCV DAAs are involved (with or without ifn or ifn+rib)?

Has VRTX itself posted SVR12 data from any of its telaprevir trials where we can compare the SVR12 numbers to the SVR24 numbers?

[DewDiligence]

Re: SVR12 vs SVR

For regimens consisting of SoC or SoC plus a single DAA, the difference between SVR12 and SVR was widely believed to be more consequential in the second-line setting than in the first-line setting. This has been stated on numerous occasions by executives (mainly the CMO’s) at such companies as VRTX and GILD.

Then along came VRTX’s PROVE-3 study, which changed the prevailing view on this subject to some degree. In the ‘12+12’ arm of PROVE-3, only one patient out of 60 who achieved SV12 failed to achieve SVR (see note 4 in #msg-36464842).

--
p.s. The original point of this thread was not the degree to which SVR12 was predictive of SVR, but rather that ANDS chose to issue a PR to report SVR12 data on only six patients. My contention is that ANDS’ PR was a pump because ANDS could simply have waited to report the SVR data (#msg-52795076).