Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C

N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953.

Abstract

Background: The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.

Methods: We provided open-label treatment to eight groups of patients. A total of 40 previously untreated patients with HCV genotype 2 or 3 infection were randomly assigned to four groups; all four groups received sofosbuvir (at a dose of 400 mg once daily) plus ribavirin for 12 weeks. Three of these groups also received peginterferon alfa-2a for 4, 8, or 12 weeks. Two additional groups of previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir monotherapy for 12 weeks or sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks. Two groups of patients with HCV genotype 1 infection received sofosbuvir and ribavirin for 12 weeks: 10 patients with no response to prior treatment and 25 with no previous treatment. We report the rate of sustained virologic response 24 weeks after therapy.

Results: Of the 40 patients who underwent randomization, all 10 (100%) who received sofosbuvir plus ribavirin without interferon and all 30 (100%) who received sofosbuvir plus ribavirin for 12 weeks and interferon for 4, 8, or 12 weeks had a sustained virologic response at 24 weeks. For the other patients with HCV genotype 2 or 3 infection, all 10 (100%) who received sofosbuvir plus peginterferon alfa-2a and ribavirin for 8 weeks had a sustained virologic response at 24 weeks, as did 6 of 10 (60%) who received sofosbuvir monotherapy. Among patients with HCV genotype 1 infection, 21 of 25 previously untreated patients (84%) and 1 of 10 with no response to previous therapy (10%) had a sustained virologic response at 24 weeks. The most common adverse events were headache, fatigue, insomnia, nausea, rash, and anemia.

Conclusions: Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection. (Funded by Pharmasset and Gilead Sciences; ClinicalTrials.gov number, NCT01260350.).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hemoglobins / metabolism
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • RNA, Viral / metabolism
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*
  • Sofosbuvir
  • Uridine Monophosphate / adverse effects
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use
  • Viral Load
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Hemoglobins
  • Interferon-alpha
  • NS-5 protein, hepatitis C virus
  • RNA, Viral
  • Recombinant Proteins
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Uridine Monophosphate
  • peginterferon alfa-2a
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT01260350