Simeprevir for the treatment of chronic hepatitis C genotype 1 infection

Expert Rev Anti Infect Ther. 2014 Aug;12(8):909-17. doi: 10.1586/14787210.2014.925800. Epub 2014 Jun 2.

Abstract

Simeprevir is a second-wave hepatitis C virus NS3/4A protease inhibitor that was designed to optimize its antiviral activity, safety, drug-drug interactions, and pharmacokinetic profile. When used to treat patients with hepatitis C virus genotype 1, simeprevir is coadministered with peginterferon and ribavirin for 12 weeks, followed by double therapy with Peg-IFN and ribavirin for an additional 12 or 36 weeks. Phase III studies achieved a sustained virologic response in 80-90% of treatment-naïve patients (International Phase III studies QUEST-1/2: 80/81%; Japanese Phase III trial CONCERTO-1: 89%). Unlike with the first protease inhibitors, telaprevir or boceprevir, used in triple therapy, when using simeprevir the frequency of clinically problematic adverse events such as anemia, rash, and digestive symptoms is almost comparable to that of double therapy. The advent of simeprevir has enabled interferon therapy, which started as monotherapy in early 1990s, to reach its maximum efficacy and arrive at what can be considered its final form at least in genotype 1b.

Keywords: Simeprevir; direct acting antiviral; hepatitis C virus; peginterferon; protease inhibitor.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / administration & dosage
  • Antiviral Agents / chemistry
  • Antiviral Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Administration Schedule
  • Drug Design
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Heterocyclic Compounds, 3-Ring / administration & dosage
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use
  • Molecular Structure
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • RNA, Viral / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use
  • Simeprevir
  • Sulfonamides / administration & dosage
  • Sulfonamides / chemistry
  • Sulfonamides / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Heterocyclic Compounds, 3-Ring
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Sulfonamides
  • Polyethylene Glycols
  • Ribavirin
  • Simeprevir
  • peginterferon alfa-2b
  • peginterferon alfa-2a