title: Telaprevir: an NS3/4A protease inhibitor for the treatment of chronic hepatitis C.
abstract: OBJECTIVE
  To review the use of telaprevir for the treatment of chronic hepatitis C.
  
  
  METHODS
  Clinical studies were identified through MEDLINE (1966-January 2011), bibliographies of articles, clinicaltrials.gov, and fda.gov, using key words VX-950, telaprevir, and chronic hepatitis C.
  
  
  METHODS
  Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of telaprevir were identified. Additional articles were identified from the bibliographies of articles retrieved through MEDLINE.
  
  
  RESULTS
  Telaprevir is an NS3/4A protease inhibitor under investigation for the treatment of chronic hepatitis C virus (HCV) with pegylated interferon and ribavirin. Telaprevir competes with viral peptide substrates for the active site of NS3 and inhibits NS3-NS4A protease activity. Telaprevir has activity against HCV genotype 1 infection in vitro and in vivo, but monotherapy results in rapid viral resistance. In 3 Phase 2 and 3 Phase 3 randomized placebo-controlled trials, 12 weeks of telaprevir, along with varying durations of ribavirin treatment, induced higher sustained virologic response (SVR) compared with ribavirin alone. SVR was approximately 70% in treatment-naïve patients, 50-60% for patients in whom SVR had not occurred with prior ribavirin treatment, and 40-45% of those who received ribavirin alone. There was a high incidence of maculopapular rash (52% in 1 trial) and anemia (27% in 1 trial) in telaprevir-treated patients. The average dropout rate in Phase 3 trials as a result of adverse effects was 13%.
  
  
  CONCLUSIONS
  Twelve weeks of telaprevir with concomitant ribavirin treatment increases SVR for treatment-naïve and non-naïve patients with genotype 1 chronic HCV compared to 48 weeks of ribavirin treatment. Telaprevir may shorten the length of ribavirin therapy for some patients with extended rapid viral response, but viral mutations, adverse effects, and a high dropout rate may reduce the SVR seen in clinical practice.
authors.affiliation: Wingate University, Wingate, North Carolina, USA. susmith@wingate.edu
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Nelson
authors.forename: Sagar
authors.initials: S
authors.lastname: Naik
authors.forename: Joanna
authors.initials: J
authors.lastname: Woten
mesh_terms: D000818:Animals; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir