Response-guided telaprevir therapy in prior relapsers? The role of bridging data from treatment-naïve and experienced subjects.

The purpose of this report is to illustrate the US Food and Drug Administration's rationale for approving response-guided therapy (RGT) for telaprevir (TVR) in combination with pegylated interferon-α and ribavirin (P/R) for the treatment of adults with genotype 1 chronic hepatitis C who were prior relapsers. RGT was prospectively evaluated in two registration trials of treatment-naïve subjects. In these studies, RGT allowed subjects who achieved undetectable hepatitis C virus RNA from weeks 4 and 12, known as extended rapid virologic response (eRVR), to stop all treatments at 24 weeks. A patient without eRVR received an additional 36 weeks of P/R after 12 weeks of a TVR triple regimen (total of 48 weeks). However, RGT in prior P/R relapsers was not prospectively evaluated. Empirical cross-trial data indicated high sustained virologic response rates (>90%) in prior relapsers achieving eRVR, irrespective of P/R duration (24 or 48 weeks). Further analyses demonstrated that interferon responsiveness does not change in P/R-experienced subjects with a second round of P/R. The comparability in interferon responsiveness across treatment courses allowed us to bridge data between treatment-naïve and P/R-experienced subjects to support the approval of RGT in prior relapse subjects.