Source

Division of Pharmacometrics, US Food and Drug Administration. Jiang.Liu@fda.hhs.gov.

Abstract

The purpose of this report is to illustrate FDA's rationale for approving response guided therapy (RGT) for telaprevir (TVR) in combination with peginterferon alfa 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 HCV 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 SVR 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 PR-experienced subjects with a second round of PR. 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. On May 23(rd) , 2011, the U.S. Food and Drug Administration (FDA) approved telaprevir (TVR) for use in combination with peginterferon alfa and ribavirin (P/R) for the treatment of genotype 1 chronic hepatitis C in adults who are either P/R treatment-naïve or -experienced(1) . TVR is an HCV NS3/4A protease inhibitor and represents a new class of small molecules that directly targets hepatitis C virus (HCV) replication(2) . The approved dosing regimen for TVR is 750 mg given three times daily for 12 weeks (T12) in combination with P/R. After reviewing the TVR new drug application (NDA), which contained 3 phase 3 studies, the FDA approved Response Guided Therapy (RGT) for treatment-naïve patients and prior P/R relapsers(3) .