Ledipasvir/sofosbuvir for treatment-naive and treatment-experienced Chinese patients with genotype 1 HCV: an open-label, phase 3b study.

ABSTRACT

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a significant medical burden in China, affecting more than 10 million persons. In clinical trials and real-world settings, treatment with ledipasvir/sofosbuvir in patients with genotype 1 HCV infection resulted in high sustained virologic response rates. Ledipasvir/sofosbuvir may provide a highly effective, short-duration, single-tablet regimen for Chinese patients with HCV infection. METHODS: Chinese patients with genotype 1 HCV infection who were HCV treatment naive or treatment experienced, without cirrhosis or with compensated cirrhosis, were treated with open-label ledipasvir/sofosbuvir for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after completing treatment (SVR12). For treatment-naive patients, SVR12 was compared to a historical rate of 57%. The primary safety endpoint was adverse events leading to permanent discontinuation of study drug; serious adverse events were also evaluated. The presence of resistance-associated substitutions (RASs) was evaluated by viral sequencing. RESULTS: All 206 enrolled patients achieved SVR12 (100%; 95% CI 98-100%), including 106 treatment-naive patients (100%; 95% CI 97-100%), which was superior to a historical SVR rate of 57% (p < 0.001). All patients with baseline NS5A and NS5B RASs (14 and 1% of patients, respectively) achieved SVR12. The most common adverse events were viral upper respiratory tract infection (17%), upper respiratory tract infection (14%), and cough (6%). There were no discontinuations due to adverse events; and no treatment-related serious adverse events were reported. CONCLUSION: Ledipasvir/sofosbuvir is a well tolerated and highly effective treatment for Chinese patients with genotype 1 HCV, regardless of prior treatment experience, cirrhosis status, or the presence of pretreatment RASs.