title: Response-guided telaprevir therapy in prior relapsers? The role of bridging data from treatment-naïve and experienced subjects.
abstract: 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.
authors.affiliation: Division of Pharmacometrics, US Food and Drug Administration, Silver Spring, MD 20993-0002, USA. jiang.liu@fda.hhs.gov
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Pravin R
authors.initials: PR
authors.lastname: Jadhav
authors.forename: Shashi
authors.initials: S
authors.lastname: Amur
authors.forename: Russell
authors.initials: R
authors.lastname: Fleischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Hammerstrom
authors.forename: Linda
authors.initials: L
authors.lastname: Lewis
authors.forename: Lisa
authors.initials: L
authors.lastname: Naeger
authors.forename: Jule
authors.initials: J
authors.lastname: O'Rear
authors.forename: Michael
authors.initials: M
authors.lastname: Pacanowski
authors.forename: Sarah
authors.initials: S
authors.lastname: Robertson
authors.forename: Shirley
authors.initials: S
authors.lastname: Seo
authors.forename: Greg
authors.initials: G
authors.lastname: Soon
authors.forename: Debra
authors.initials: D
authors.lastname: Birnkrant
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D017277:Drug Approval / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000592:standards; D019317:Evidence-Based Medicine / Q000379:methods; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000627:therapeutic use*; D012254:Ribavirin / Q000627:therapeutic use; D055502:Secondary Prevention; D014481:United States
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir