Safety and efficacy of faldaprevir with pegylated interferon alfa-2a and ribavirin in Japanese patients with chronic genotype-1 hepatitis C infection

Background & Aims Faldaprevir (BI 201335) is a potent once-daily (QD) NS3/4A protease inhibitor for the treatment of patients with genotype-1 (GT-1) hepatitis C virus (HCV). The aim of this study was to evaluate the safety, pharmacokinetics and efficacy of faldaprevir plus pegylated interferon alfa-2a (PegIFN) and ribavirin (RBV) in Japanese patients infected with chronic GT-1 HCV. Methods Part 1 of this phase II study was a randomized, double-blind, placebo-controlled, dose-ascending study. Treatment-naive patients received faldaprevir 120 or 240 mg QD, or placebo, plus PegIFN/RBV for 4 weeks, then PegIFN/RBV alone for 44 weeks. In Part 2 (open label), treatment-experienced patients received faldaprevir 240 mg QD plus PegIFN/RBV for 4 weeks, then PegIFN/RBV alone for 44 weeks. Efficacy was assessed using sustained virological response (SVR) 24 weeks after treatment completion. The pharmacokinetics, safety and tolerability of faldaprevir were also assessed. Results SVR was achieved by 4/6 (67%) treatment-naive patients treated with faldaprevir 120 mg QD, 5/6 (83%) patients treated with faldaprevir 240 mg QD and 2/4 (50%) patients who received placebo. Of the treatment-experienced patients, 3/6 (50%) achieved SVR. Faldaprevir was well tolerated. There was one serious adverse event, which was not considered to be treatment related. Rash and hyperbilirubinaemia were more frequently reported with faldaprevir than with placebo in treatment-naive patients, but no cases were severe or serious and none led to discontinuation. Steady-state plasma concentrations of faldaprevir were reached within 7 days of QD dosing. Conclusions Faldaprevir with PegIFN/RBV was efficacious and well tolerated, supporting further evaluation of this combination in Japanese patients.