title: Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent.
abstract: OBJECTIVE
  The Phase-2 C-SALVAGE study evaluated an investigational interferon-free combination of grazoprevir (a NS3/4A protease inhibitor) and elbasvir (a NS5A inhibitor) with ribavirin for patients with chronic HCV genotype-1 infection who had failed licensed DAA-containing therapy.
  
  
  METHODS
  C-SALVAGE was an open-label study of grazoprevir 100 mg and elbasvir 50 mg QD with weight-based ribavirin BID for 12 weeks in cirrhotic and non-cirrhotic patients with chronic HCV genotype-1 infection who had not attained SVR after ⩾4 weeks of peginterferon and ribavirin plus either boceprevir, telaprevir, or simeprevir. Exclusion criteria included decompensated liver disease, hepatocellular carcinoma, and HIV or HBV co-infection. The primary efficacy outcome was SVR12 defined as a HCV RNA level below the assay limit of quantification 12 weeks after the end of treatment.
  
  
  RESULTS
  Of the 79 patients treated with ⩾1 dose of study drug, 66 (84%) patients had a history of virologic failure on a regimen containing a NS3/4A protease inhibitor; 12 of the other 13 patients discontinued prior treatment because of adverse experiences. At entry, 34 (43.6%) of 78 evaluable patients harbored NS3 RAVs. SVR12 rates were 76/79 (96.2%) overall, including 28/30 (93.3%) patients with genotype 1a infection, 63/66 (95.5%) patients with prior virologic failure, 43/43 (100%) patients without baseline RAVs, 31/34 (91.2%) patients with baseline NS3 RAVs, 6/8 (75.0%) patients with baseline NS5A RAVs, 4/6 (66.7%) patients with both baseline NS3 and RAVs, and 32/34 (94.1%) cirrhotic patients. None of the five reported serious adverse events were considered drug-related.
  
  
  CONCLUSIONS
  Grazoprevir and elbasvir plus ribavirin for 12 weeks provides a promising new treatment option for patients after failure of triple therapy containing an earlier-generation protease inhibitor.
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain. Electronic address: xforns@clinic.ub.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Henry Ford Health System, Detroit, MI, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.affiliation: Carmel Medical Center, Haifa, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Zuckerman
authors.affiliation: The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: Servicio de Gastroenterología y Hepatología, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gilbert
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: John
authors.initials: J
authors.lastname: Palcza
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Anita Y M
authors.initials: AY
authors.lastname: Howe
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Wahl
authors.affiliation: Merck and Co., Inc., Kenilworth, NJ, USA.
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
authors.affiliation: Hospital Universitario Valle Hebron and Ciberehd, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001572:Benzofurans / Q000008:administration & dosage; D002219:Carbamates; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011810:Quinoxalines / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D013449:Sulfonamides; D017211:Treatment Failure; D047029:Lactams, Macrocyclic
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D007093:Imidazoles; D011810:Quinoxalines; D012254:Ribavirin; D013449:Sulfonamides; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir
keywords: C-SALVAGE; Direct-acting antiviral agents; Elbasvir; Grazoprevir; HCV genotype-1