Ombitasvir: a potent pan-genotypic inhibitor of NS5A for the treatment of hepatitis C virus infection

Expert Rev Anti Infect Ther. 2014 Sep;12(9):1033-43. doi: 10.1586/14787210.2014.940898. Epub 2014 Jul 30.

Abstract

Hepatitis C virus (HCV) chronically infects about 150,000,000 people worldwide and is a relevant cause of liver cirrhosis, hepatocellular carcinoma and death. Antiviral treatment is rapidly moving from interferon (IFN)-based therapy to IFN-free approaches. This review focuses on the mechanism of action, pharmacokinetics, efficacy, tolerability, safety and resistance of ombitasvir, which is an inhibitor of the HCV nonstructural protein 5A. The pharmacokinetics of ombitasvir enables its once daily administration. In vivo, in combinations with other oral direct acting antivirals, ombitasvir achieves very high rates of sustained virological response (about 95%) in patients with HCV genotype 1 infection with a good tolerability. Resistance profiling revealed a low barrier to resistance when given as monotherapy. However, coadministration of ombitasvir and other antivirals enhances its barrier to resistance. In conclusion, ombitasvir is a good drug to be used in IFN-free combinations for the treatment of chronic hepatitis C.

Keywords: ABT-450; NS5A; dasabuvir; interferon-free; ombitasvir; pegylated-interferon; resistance; ribavirin.

Publication types

  • Review

MeSH terms

  • Anilides / administration & dosage
  • Anilides / adverse effects
  • Anilides / pharmacokinetics
  • Anilides / therapeutic use*
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • Carbamates / administration & dosage
  • Carbamates / adverse effects
  • Carbamates / pharmacokinetics
  • Carbamates / therapeutic use*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / metabolism
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology
  • Humans
  • Proline
  • RNA, Viral / blood
  • Valine
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • RNA, Viral
  • Viral Nonstructural Proteins
  • ombitasvir
  • Proline
  • NS-5 protein, hepatitis C virus
  • Valine