Sofosbuvir/Velpatasvir for Treatment of Hepatitis C Virus in Asia: An Open-Label, Phase 3 Study

Background: Treatment with sofosbuvir/velpatasvir has resulted in high sustained virologic response rates in HCV-infected patients with genotype 1 to 6 in clinical trials and real-world settings, but its efficacy and safety has not been assessed in Asia, a region with diverse HCV genotypes. Methods: Patients in China, Thailand, Vietnam, Singapore, and Malaysia with genotype 1-6 HCV infection who were HCV treatment naive or treatment experienced, without cirrhosis or with compensated cirrhosis, were treated with open-label sofosbuvir/velpatasvir for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after completing treatment (SVR12). The primary safety endpoint was adverse events leading to premature discontinuation of study drug; serious adverse events were also evaluated. The presence of resistance-associated substitutions (RASs) was evaluated by viral sequencing. Findings: Of the 375 patients in the study, 362 patients (97%) achieved SVR12 (95% CI: 94.1% to 98.1%). The SVR12 rate was >99% for patients with genotype 1, 2, or 6 HCV infection and 86% for patients with genotype 3. Among patients with genotype 3b, nearly all of whom had baseline NS5A RASs, the SVR12 rate was 89% in noncirrhotics (25 of 28 patients) and 50% in cirrhotics (7 of 14 patients). Overall, 47% of patients had baseline NS5A RASs, 94% of whom achieved SVR12. The most common adverse events were upper respiratory tract infection (10%) and headache (5%). There were no discontinuations due to adverse events; serious adverse events were reported in 3 patients (0.8%), none of which were assessed by the investigator as related to sofosbuvir/velpatasvir treatment. Interpretation: Consistent with data from Phase 3 studies, treatment with the single-tablet regimen of sofosbuvir/velpatasvir for 12 weeks provided high overall SVR12 rates in Asian patients, but those with genotype 3b and cirrhosis had lower rates of SVR12. Trial Registration Number: NCT02671500 Funding: Funding for this study was provided by Gilead Sciences. Declaration of Interest: Lai WEI has received research funding from AbbVie, Bristol-Myers Squibb, and Roche. Teerha PIRATVISUTH has served on advisory boards for Bristol-Myers Squibb, Bayer, and Mylan, has served as a speaker for Bristol-Myers Squibb, MSD, Bayer, and Mylan, and has received research funding from Bristol-Myers Squibb, Gilead, MSD, Fibrogen, and Bayer. Chee-Kiat TAN has served on advisory boards and as a speaker for Gilead. Luisa M. STAMM, Sophia LU, Hadas DVORY-SOBOL, Hongmei MO, and Diana M. BRAINARD are employees of and hold stock in Gilead. The remaining authors declare no conflicts of interest. Ethical Approval: Prior to enrollment and before any study procedures were conducted, written informed consent was obtained from all patients. The study was approved by the independent ethics committees at all participating sites and was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice.