Glecaprevir/pibrentasvir for the treatment of chronic hepatitis C: design, development, and place in therapy

Drug Des Devel Ther. 2019 Jul 29:13:2565-2577. doi: 10.2147/DDDT.S172512. eCollection 2019.

Abstract

Direct-acting antiviral (DAA) therapy has changed the landscape of hepatitis C virus (HCV) management and has changed the focus to the possibility of HCV elimination in the near future. Glecaprevir, an NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor, have addressed many of the existing shortcomings in the DAA therapy spectrum. This combination has proven to be a highly efficacious pan-genotypic DAA with a high barrier to resistance as a once-daily, all-oral medication. This review explores the design and development of glecaprevir and pibrentasvir, its place in current HCV management in the midst of a myriad of DAA therapy options, and also remaining challenges.

Keywords: direct-acting antiviral therapy; glecaprevir; hepatitis C virus; pibrentasvir.

Publication types

  • Review

MeSH terms

  • Aminoisobutyric Acids
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Cyclopropanes
  • Drug Design*
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Proline / analogs & derivatives
  • Pyrrolidines
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology*
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • Proline
  • Leucine
  • glecaprevir