title: Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials.
abstract: OBJECTIVE
  Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection.
  
  
  METHODS
  Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12).
  
  
  RESULTS
  SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively.
  
  
  CONCLUSIONS
  Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.
authors.affiliation: University of Chicago Medicine, Chicago, IL, USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Jensen
authors.affiliation: Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRB3, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4 Queen Mary University of London, London, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.affiliation: Queen Mary University of London, London, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: J.W.Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA.
authors.forename: Parvez
authors.initials: P
authors.lastname: Mantry
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.affiliation: CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Institut Arnault Tzanck, St. Laurent du Var, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Ouzan
authors.affiliation: Wellcome Trust Clinical Research Facility, Southampton, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Wright
authors.affiliation: Hospital Meixoeiro, Vigo, Spain.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Morano
authors.affiliation: Northwest Indiana Center for Clinical Research, Valparaiso, IN, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Buynak
authors.affiliation: Hopital Saint Joseph, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.affiliation: Southern California Liver Centers, Coronado, CA, USA.
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.affiliation: Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.affiliation: Yamanashi Central and Kita Hospitals, Yamanashi, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.affiliation: Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.
authors.forename: Seung W
authors.initials: SW
authors.lastname: Paik
authors.affiliation: Toronto Western Hospital Liver Center, Toronto, ON, Canada.
authors.forename: David K
authors.initials: DK
authors.lastname: Wong
authors.affiliation: LAIR Centre, Vancouver, BC, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Tam
authors.affiliation: HSC University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Kaita
authors.affiliation: Hepatitis Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: S Victor
authors.initials: SV
authors.lastname: Feinman
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.forename: Joseph
authors.initials: J
authors.lastname: Scherer
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Quinson
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Voss
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Gallivan
authors.affiliation: Afiliacja Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Wulf O
authors.initials: WO
authors.lastname: Böcher
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: D000328:Adult; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000031:analogs & derivatives; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D015415:Biomarkers; D002352:Carrier Proteins; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011392:Proline; D011480:Protease Inhibitors; D011804:Quinolines; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C552340:faldaprevir; C100416:peginterferon alfa-2a