title: Once-daily simeprevir with peginterferon and ribavirin for treatment-experienced HCV genotype 1-infected patients in Japan: the CONCERTO-2 and CONCERTO-3 studies.
abstract: BACKGROUND
  Efficacy of available therapies for patients with HCV who have previously failed treatment is limited. Two Phase III, open-label trials in Japan investigated efficacy and safety of simeprevir and peginterferon-α-2a/ribavirin (PR) combination therapy in treatment-experienced patients with genotype 1 HCV infection.
  
  
  METHODS
  In CONCERTO-2, prior non-responders to IFN-based therapy (N = 106) received simeprevir (TMC435) 100 mg QD with PR for 12 (SMV12, n = 53) or 24 weeks (SMV24, n = 53) followed by response-guided therapy (RGT) with PR for 12/36 (SMV12) or 0/24 (SMV24) weeks. In CONCERTO-3, relapsers after IFN-based therapy (N = 49) received simeprevir 100 mg QD with PR for 12 weeks followed by RGT with PR for 12/36 weeks. Primary endpoints were the rates of sustained virologic response 12 weeks after treatment end (SVR12).
  
  
  RESULTS
  SVR12 rates were 52.8% (SMV12) and 35.8% (SMV24) for prior non-responders, and 95.9% for prior relapsers (SMV12; p ≤ 0.0001 vs null hypothesis, respectively). Most prior non-responders (SMV12: 81.1%; SMV24: 73.6%) and prior relapsers (95.9%) met RGT criteria and completed PR to Week 24. Of these, 60.5%, 48.7%, and 95.7%, respectively, achieved SVR12. Viral breakthrough occurred in 13.2 % (SMV12) and 11.3% (SMV24) of prior non-responders; no viral breakthrough occurred in prior relapsers. Viral relapse occurred in 38.6% (SMV12) and 51.1% (SMV24) of prior non-responders and 8.2% of prior relapsers. Simeprevir with PR was generally well tolerated in both studies.
  
  
  CONCLUSIONS
  Re-treatment with 12 weeks of simeprevir QD with PR provided high SVR in treatment-experienced patients with chronic HCV genotype 1 infection, and allowed most patients to complete treatment in 24 weeks.
authors.affiliation: Musashino Red-Cross Hospital, Tokyo, Japan, nizumi@musashino.jrc.or.jp.
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Mai
authors.initials: M
authors.lastname: Kato
authors.forename: Rito
authors.initials: R
authors.lastname: Ki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Komada
authors.forename: Chiharu
authors.initials: C
authors.lastname: Seto
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000069616:Simeprevir; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a