title: A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV.
abstract: Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study evaluated the safety and efficacy of filibuvir plus pegylated interferon alfa-2a (pegIFN)/ribavirin.
  
  
  
  Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg twice daily (BID) or placebo plus pegIFN (180 μg/wk) and ribavirin (1,000/1,200 mg BID) for 24 weeks. Filibuvir patients who achieved defined response through week 24 discontinued therapy at week 24. All other patients continued on open-label pegIFN/ribavirin through week 48. The primary endpoint was the proportion of patients who achieved sustained virologic response (SVR) defined as HCV RNA < 15 IU/mL at end of treatment (weeks 24 or 48) and week 72.
  
  
  
  Overall, 288 patients were randomized and treated. SVR was achieved by 41.7, 39.6, and 45.8% of patients in the filibuvir 300 mg, 600 mg, and placebo arms, respectively. While the addition of filibuvir to pegIFN/ribavirin improved on-treatment virologic response parameters, this did not translate into improved SVR rates due to a high rate of virologic relapse following completion of therapy (300 mg: 35.9%; 600 mg: 42.9%; placebo: 25.4%). The most commonly reported adverse events were nausea, fatigue, headache, and insomnia, and were reported at similar rates across arms.
  
  
  
  Filibuvir plus pegIFN/ribavirin did not improve the percentage of patients achieving SVR compared with administration of pegIFN/ribavirin alone. However, the agent was well tolerated and was associated with higher on-treatment virologic response parameters. Further evaluation of filibuvir in combination with other direct-acting antiviral agents may be considered.
authors.affiliation: Fundación de Investigación and San Juan Bautista School of Medicine, San Juan, Puerto Rico, USA.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.affiliation: University of British Columbia and Vancouver General Hospital, Vancouver, B.C. Canada.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, Université Paris-Diderot, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Pfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USA. No longer affiliated with Pfizer.
authors.forename: Subasree
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Pfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USA. No longer affiliated with Pfizer.
authors.forename: Vivek S
authors.initials: VS
authors.lastname: Purohit
authors.affiliation: Pfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USA. No longer affiliated with Pfizer.
authors.forename: Cunshan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Pfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USA. No longer affiliated with Pfizer.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hammond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011753:Pyrones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult; D011743:Pyrimidines
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011753:Pyrones; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D014230:Triazoles; C550357:filibuvir; D011743:Pyrimidines; C100416:peginterferon alfa-2a