Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 (GT1b) infection: Phase 3 studies.

Background And Aim: Vaniprevir is a macrocyclic hepatitis C virus (HCV) non-structural (NS)3/4A protease inhibitor. The objective of these phase 3 multicenter, open-label trials was to evaluate the safety and efficacy of vaniprevir + peginterferon alfa-2b + ribavirin (PR) in Japanese patients with HCV genotype (GT)1 infection who had previously failed treatment with interferon-based regimens.

Methods: Japanese patients with chronic HCV GT1 were enrolled. In PN044, patients with previous relapse or virologic breakthrough were randomized to vaniprevir (300 mg twice daily) + PR for 12 weeks followed by PR for another 12 weeks (12-week arm) or vaniprevir + PR for 24 weeks (24-week arm). In PN045, patients with previous partial/null response received vaniprevir + PR for 24 weeks. The primary endpoint was sustained virologic response at 24 weeks after completing treatment (SVR ).

Results: In PN044 (n = 51), SVR was 92.0% and 96.2% in the 12- and 24-week arms, respectively. In PN045 (n = 42), SVR was 61.9% in all patients and 55.2% in previous null responders. In both studies, vaniprevir + PR was generally safe and well tolerated; the majority of adverse events were mild/moderate and included pyrexia, decreased hemoglobin, headache, nausea, pruritus, and decreased platelet count. Polymorphisms in the HCV NS3 gene at baseline (Y56, Q80, and V170) did not impact treatment outcome. Virologic failure was principally associated with the on-treatment emergence of R155 or D168 mutations.

Conclusions: Vaniprevir + PR is an effective, well-tolerated treatment for Japanese patients with HCV GT1 infection who failed previous interferon-based treatment. ClinicalTrials.gov Identifier NCT01405937 and NCT01405560 (Protocols PN044 and PN045).