Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.

Abstract

Background: In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.

Methods: We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy.

Results: Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia.

Conclusions: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Carbamates / adverse effects
  • Carbamates / therapeutic use*
  • Drug Combinations
  • Drug Resistance, Viral
  • Female
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Heterocyclic Compounds, 4 or More Rings / adverse effects
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use*
  • Humans
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Sofosbuvir / adverse effects
  • Sofosbuvir / therapeutic use*
  • Treatment Outcome
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Drug Combinations
  • Heterocyclic Compounds, 4 or More Rings
  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • velpatasvir
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02201953
  • ClinicalTrials.gov/NCT02220998