Ledipasvir: a novel synthetic antiviral for the treatment of HCV infection

Abstract

Introduction: About 150,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). HCV infection can lead to liver cirrhosis, hepatocellular carcinoma and death. Treatment was based previously only on pegylated interferon combined with other antiviral drugs. Recently, the first interferon-free combination for patients with genotype 2 or 3 was approved in the USA and Europe, and several molecules are in an advanced phase of clinical development.

Areas covered: This review focuses on the pharmacokinetics, pharmacodynamics and tolerability of ledipasvir, an inhibitor of HCV nonstructural 5A protein. The authors also highlight the drug's safety and resistance profile.

Expert opinion: The pharmacokinetic profile and antiviral activity of ledipasvir are ideal. However, given the high rate of natural and drug-related ledipasvir-resistant HCV mutations, ledipasvir is administered in combination regimens with other antiviral drugs, which resulted in a cure rate up to 100%. While ledipasvir is effective in patients with genotype 1 chronic hepatitis C, its efficacy remains to be established in patients with genotype 4, 5 or 6, in subjects with HIV coinfection, in hemodialyzed and elderly patients and in subjects with decompensated cirrhosis. If the excellent results of combination therapy be confirmed in larger trials, hepatologists will have the possibility to cure most HCV-positive patients in the near future.

Keywords::

• GS-5885
• ledipasvir
• pegylated interferon
• resistance
• ribavirin
• sofosbuvir
• tolerability

Acknowledgements

Authors are grateful to JA Gilder (Scientific Communication srl., Naples, Italy) for text editing.

Declaration of interest

G Castaldo and F Borgia are employees of CEINGE Advanced Biotechnologies. The authors declare that they have no conflict of interest and they have received no payment in the preparation of their manuscript.