Z Gastroenterol 2014; 52 - P53
DOI: 10.1055/s-0034-1376037

Simeprevir (TMC435) with Peginterferon/Ribavirin for treatment of chronic HCV genotype 1 infection in treatment-naïve european patients in the quest-1 and quest-2 phase III trials

M Gschwantler 1, GR Foster 2, IM Jacobson 3, GJ Dore 4, M Fried 5, M Manns 6, P Marcellin 7, F Poordad 8, ES de Araujo 9, M Peeters 10, O Lenz 10, S Ouwerkerk-Mahadevan 11, G De La Rosa 12, R Kalmeijer 13, M Beaumont-Mauviel 10
  • 1Wilhelminenspital, Department of Internal Medicine IV, Vienna, Austria
  • 2Queen Mary's University of London, London, United Kingdom
  • 3Weill Cornell Medical College, New York, United States
  • 4The Kirby Institute, University of New South Wales, Darlinghurst, Australia
  • 5University of North Carolina and Chapel Hill, North Carolina, United States
  • 6Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Germany
  • 7Hopital Beaujon, Service d'Hépatologie, INSERM U-481, Clichy, France
  • 8Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States
  • 9Hospital das Clinicas of the University of Sao Paulo School of Medicine, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil
  • 10Janssen Infectious Diseases BVBA, Beerse, Belgium
  • 11Janssen Research & Development, Beerse, Belgium
  • 12Janssen Global Services, LLC, Titusville, United States
  • 13Janssen Research & Development, Titusville, United States

Background/aims: Simeprevir (SMV) is a one pill, once-daily (QD), oral HCV NS3/4A protease inhibitor. QUEST-1 and QUEST-2 were randomised, double-blind, Phase III trials evaluating SMV plus peginterferon α-2a (QUEST-1) or peginterferon α-2a/2b (QUEST-2) plus ribavirin (PR) versus placebo (PBO)/PR in treatment-naïve genotype (GT) 1 HCV patients. Pooled efficacy and safety data from QUEST-1/QUEST-2 are presented for European patients.

Methods: Patients received SMV 150 mg QD (12wks) with PR (24 or 48 wks; based on response-guided therapy, RGT), or PBO (12wks) plus PR (48wks). Primary efficacy endpoint: sustained virological response at 12wks (SVR12).

Results: 418/785 (53.2%) patients were European (male: 57.7%, white 96.4%, HCV GT1a/1b 30.1/68.7%, 5.3% GT1a Q80K, IL28B CC/CT/TT 28.0/59.8/12.2%, METAVIR F3/F4 12.7/7.3%). SVR12 was higher with SMV/PR versus PBO/PR in European patients overall (80.4% vs. 50.0%; p < 0.001) and by patient sub-group. 91.3% of SMV/PR-treated patients were eligible for 24 weeks of PR; 91.7% of these patients achieved SVR12. 82.2% and 13.7% of SMV/PR- and PBO/PR-treated patients, respectively, achieved rapid virological response. Fewer SMV/PR-treated patients experienced on-treatment failure (5.8% vs. PBO/PR 29.6%) or viral relapse (8.1% vs. PBO/PR 24.2%). During SMV/PR treatment (Wks 1 – 12), 62.0% of patients had ≥1 AE possibly SMV-related. AEs (SMV/PR group) were mostly Grade 1/2 (Grade 3/4, 25.0%). SAEs possibly SMV-related (0.4%) and SMV discontinuations due to ≥1 AE (2.2%) were infrequent. No fatal AEs occurred.

Conclusion: SMV/PR confers clinical benefit versus PBO/PR and is well tolerated in European HCV GT1-infected patients.

Acknowledgements: This study was supported by Janssen Research & Development, Beerse, Belgium