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

Abstract

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 24 ). Results: In PN044 (n = 51), SVR 24 was 92.0% and 96.2% in the 12-and 24-week arms, respectively. In PN045 (n = 42), SVR 24 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.

Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus‐infected patients with renal impairment

“…Telaprevir and boceprevir, first‐generation HCV protease inhibitors, are associated with severe adverse events, including dermatological reactions and renal impairment in triple therapy with pegylated‐IFN and ribavirin. In contrast, the second‐generation protease inhibitors simeprevir and vaniprevir are not associated with these adverse events in triple therapy with pegylated‐IFN and ribavirin. The different adverse event profiles might be related to the difference in protease inhibitor class.…”

Treatment progress and expansion in Japan: From interferon to direct-acting antiviral

“…protease inhibitor, vaniprevir (VAN), for 12 weeks plus Peg-IFN and RBV combination therapy for 24 weeks was developed. SVR rates for treatment-naïve patients and relapsers to previous therapy were 84% and 92%, respectively, and the profile of adverse events in patients who were treated with this combination was comparable to those who were treated with Peg-IFN and RBV combination (35,36). In this triple therapy, patients with partial (detectable but decreased by more than 2 log 10 in HCV-RNA after 12 weeks of therapy) or null response (detectable and decreased by less than 2 log 10 in HCV-RNA after 12 weeks of therapy) to previous therapy were treated with VAN plus Peg-IFN and RBV combination therapy for 24 weeks.…”

“…In this triple therapy, patients with partial (detectable but decreased by more than 2 log 10 in HCV-RNA after 12 weeks of therapy) or null response (detectable and decreased by less than 2 log 10 in HCV-RNA after 12 weeks of therapy) to previous therapy were treated with VAN plus Peg-IFN and RBV combination therapy for 24 weeks. SVR rates were 62% in patients with partial or null responses to previous therapy and 55% in patients only with a null response to previous therapy (36).…”