There may be new options available soon for the treatment of hepatitis C (HCV). In a company-sponsored study, patients with HCV genotype 1, 2, 4, or 6 were randomized to sofosbuvir plus a new NS5A inhibitor velpatasvir or matching placebo. Nearly half of the 700 treated patients had genotype 1a or 1b, while 17% had genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. An additional group of 35 patients with genotype 5 were not randomized because of the very low prevalence of this type of HCV. One-third of all patients had been previously treated and 19% had cirrhosis. The overall sustained virologic response (SVR) at 12 weeks after end of therapy was 99% (95% confidence interval [CI], 98 to > 99). Serious adverse events were reported in 2% of the treatment group. The authors concluded that once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of SVR in both previously treated and treatment-naïve patients with HCV genotypes 1, 2, 4, 5, or 6, including patients with cirrhosis. (N Engl J Med 2015 Nov 16. doi:1056/NEJMoa1512610.)
A second trial used the same combination with and without ribavirin in 267 patients with decompensated cirrhosis across the same genotypes (78% genotype 1). In this trial, patients were assigned in a 1:1:1 ratio to sofosbuvir-velpatasvir once daily for 12 weeks or 24 weeks, or 12 weeks of sofosbuvir-velpatasvir plus ribavirin. Overall, SVR was 83% (95% CI, 74-90) for 12 weeks of sofosbuvir-velpatasvir, 94% (95% CI, 87-98) for sofosbuvir-velpatasvir plus ribavirin, and 86% (95% CI, 77-92) for 24 weeks of sofosbuvir-velpatasvir. A post-hoc analysis did not detect a significant difference in SVR among the three groups. Adverse events were similar for the three groups, although there was a higher frequency of anemia with ribavirin. The authors concluded that sofosbuvir-velpatasvir with or without ribavirin for 12 weeks or sofosbuvir-velpatasvir alone for 24 weeks resulted in high rates of SVR in patients with HCV and decompensated cirrhosis (N Engl J Med 2015 Nov 16. doi:10.1056/NEJMoa1512614). Both trials were sponsored by Gilead, the manufacturer of sofosbuvir/ledipasvir (Harvoni), which is approved for treatment of HCV genotype 1.