The same HCV RNA IWR-1 chemical structure assay was used for Studies P05216, C216, and 108, so we are not aware of an obvious, biologically plausible explanation for a higher

rate of transient detectable/BLOQ HCV RNA levels during follow-up among SVR subjects in Study 108. However, both P05216 and C216 used the same contract laboratory for HCV RNA analyses, whereas a different contract laboratory was used for Study 108. Differences in assay performance related to the specific laboratory performing the analyses could be a possible explanation of different reporting frequencies of low level, detectable HCV RNA. As shown in Table 2, among subjects who achieved SVR (based on

at any point during follow-up, and less than 1% of all follow-up results from SVR-achieving subjects were reported as detectable. All of these detectable HCV RNA measures were either below or near the assay LLOQ. In contrast to the Vendor A results reported for C216 and P05216, for Study 108, Vendor B reported a 9% frequency (>15- and 45-fold higher than P05216 and C216, respectively) of detectable follow-up Galunisertib in vivo HCV RNA among SVR-achieving subjects, representing 24% of all SVR subjects (Table 2). As in C216 and P05216, all of these detectable HCV RNA measures were either below or near the assay LLOQ. Reanalyses conducted by Vendor A for a subset of Study 108 samples from follow-up and various on-treatment timepoints yielded a reduced frequency of detectable/BLOQ HCV RNA results. The extent of this reduced frequency of detectable/BLOQ results varied by timepoint. For samples reported as detectable/BLOQ by Vendor B, 40% and 70% of those from week 4 and week 12 on-treatment timepoints, respectively, and 92% for follow-up timepoints, were reported by Vendor A as undetectable. Taken together, the higher

frequency of follow-up detectable/BLOQ results from SVR subjects Tryptophan synthase reported by Vendor B for Study 108 correlated with the higher frequency of detectable/BLOQ results reported during treatment, and was associated with less difference in SVR rates based on detectable/BLOQ versus undetectable HCV RNA during treatment. Our analyses of boceprevir and telaprevir clinical trials indicate that undetectable and detectable/BLOQ HCV RNA levels during treatment are qualitatively different, and this difference is clinically relevant. An on-treatment HCV RNA level that is detectable/BLOQ is, on average, indicative of a reduced virologic response compared with an HCV RNA level that is undetectable at the same timepoint.