Faldaprevir (BI 201335), BI 207127 and ribavirin oral therapy for treatment-naive HCV genotype 1 : SOUND-C1 final results

BACKGROUND: Faldaprevir (BI 201335) and BI 207127 are direct-acting antiviral agents under development for the treatment of chronic hepatitis C virus infection. This article describes the final results of the phase 1b SOUND-C1 study which evaluated the interferon-free oral combination of faldaprevir, BI 207127, and ribavirin in 32 treatment-naive patients infected with hepatitis C virus genotype 1. METHODS: Patients were randomized to receive BI 207127 400 mg (n=15) or 600 mg (n=17) three times daily plus faldaprevir 120 mg once daily and weight-based ribavirin for 4 weeks. Interferon-free therapy was followed by response-guided faldaprevir plus pegylated interferon alfa-2a/ribavirin to week 24 or 48. RESULTS: At week 4, 73% (11/15) and 100% (17/17) of patients in the BI 207127 400 mg and 600 mg groups achieved hepatitis C virus (HCV) RNA >25 IU/mL, respectively. During interferon-free treatment, virological breakthrough was reported in one patient and re-increase of HCV RNA in one patient. Both patients were successfully treated with interferon-containing therapy. The rate of sustained virological response 24 weeks after completion of treatment was 73% (11/15) in the BI 207127 400 mg group and 94% (16/17) in the 600 mg group. During faldaprevir plus pegylated interferon alfa-2a/ribavirin treatment, the most common adverse events were pruritus (38% of patients), rash (31%), and asthenia (31%); these were severe in approximately 3% of patients. CONCLUSIONS: Potent antiviral activity and favourable safety of the treatment regimen were demonstrated. Furthermore, the results suggest that patients with breakthrough at week 4 may be rescued with an interferon-containing regimen.