Sofosbuvir and Ledipasvir/Sofosbuvir for the treatment of patients with Chronic Genotype 6 Hepatitis C Virus Infection: integrated analysis of Phase 2 and Phase 3 studies

Abstract

INTRODUCTION: Chronic HCV infection is endemic in South East Asia with HCV genotype 6 (GT6) accounting for 18-49% of those infected. In the US and Canada, nearly one-third of immigrants from Southeast Asia with HCV are infected with GT6. Few studies have examined the efficacy and safety of direct acting antiviral (DAA) regimens in GT6 infected patients. The aim of this integrated analysis was to characterize the efficacy and safety of sofosbuvir (SOF)-based regimens in patients with chronic GT6 HCV infection. METHODS: GT6 infected subjects were identified in 5 studies (ATOMIC, NEUTRINO, GS-US-334-0115, ELECTRON2, GS-US-337-0131) and are included in this analysis. Treatment-naïve or treatment-experienced patients received SOF+RBV±Peg-IFNα or ledipasvir (LDV)/SOF for 12-24 weeks. The primary efficacy endpoint in all studies was SVR12. RESULTS: A total of 52 subjects with GT6 HCV infection were identified. The majority were treatment-naïve (94%), Asian (81%), male (58%), and had IL28B CC alleles (81%). The mean age was 50 years (range 26-76) and 10% had cirrhosis. GT6 subtypes included 6a, 6a/b, 6c-1, 6e, 6g, 6j, 6l, 6m, 6o, 6p, 6q, and 6r. The table below presents SVR12 by regimen. One subject in ELECTRON2 withdrew consent after receiving 8 weeks of LDV/SOF and relapsed with the emergent NS5B RAV S282T. All remaining 51 patients achieved SVR12, including 100% (3/3) experienced and 100% (5/5) cirrhotics. CONCLUSIONS: SOF+RBV±Peg-IFNα and LDV/SOF regimens are well-tolerated and highly effective in patients with chronic GT6 HCV infection including those who are treatment experienced and have compensated cirrhosis. These regimens provide multiple therapeutic options for consideration when evaluating optimal therapy for individual patients with chronic GT6 HCV infection. (diagram see journal abstracts)