Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection

N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.

Abstract

Background: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.

Methods: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.

Results: Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea.

Conclusions: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Drug Combinations
  • Female
  • Fluorenes / administration & dosage
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use*
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • Nucleotidyltransferases / antagonists & inhibitors
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • Sofosbuvir
  • Uridine Monophosphate / administration & dosage
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Drug Combinations
  • Fluorenes
  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • ledipasvir
  • Uridine Monophosphate
  • Nucleotidyltransferases
  • ribonucleotide polymerase
  • RNA-Dependent RNA Polymerase
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT01768286