Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection

N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.

Abstract

Background: In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.

Methods: We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily 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: Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea.

Conclusions: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Fluorenes / adverse effects
  • Fluorenes / therapeutic use*
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use
  • Sofosbuvir
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • RNA, Viral
  • ledipasvir
  • Ribavirin
  • Uridine Monophosphate
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT01701401