title: Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial.
abstract: Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin (PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks' treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%; P = 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively.
  
  
  CONCLUSIONS
  Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial responders. The 240 mg QD dose is currently undergoing phase 3 evaluation.
authors.affiliation: Viral Hepatitis Center, John Hopkins University School of Medicine, Baltimore, MD, USA. msulkowski@jhmi.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Shafran
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Yakov
authors.initials: Y
authors.lastname: Datsenko
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
authors.forename: George
authors.initials: G
authors.lastname: Kukolj
authors.forename: Joseph
authors.initials: J
authors.lastname: Scherer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Nehmiz
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Steinmann
authors.forename: Wulf O
authors.initials: WO
authors.lastname: Böcher
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; 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; C100416:peginterferon alfa-2a