Z Gastroenterol 2014; 52 - P61
DOI: 10.1055/s-0034-1376045

Simeprevir (TMC435) with Peginterferon/Ribavirin for treatment of chronic HCV genotype 1 infection in european patients who relapsed after previous interferon-based therapy: the promise trial

P Ferenci 1, X Forns 2, E Lawitz 3, S Zeuzem 4, EJ Gane 5, JP Bronowicki 6, P Andreone 7, A Horban 8, AS Brown 9, M Peeters 10, O Lenz 10, S Ouwerkerk-Mahadevan 11, G De La Rosa 12, R Kalmeijer 13, M Beaumont-Mauviel 10
  • 1Medical University Vienna, Department of Internal Medicine IV, Austria, Vienna, Austria
  • 2Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
  • 3Texas Liver Institute, University of Texas Health Science Center, San Antonio, United States
  • 4J.W. Goethe University Hospital, Frankfurt, Germany
  • 5Auckland Hospital Clinical Studies Unit, Auckland, New Zealand
  • 6INSERM U954, Université de Lorraine, Centre Hospitalier Universitaire de Nancy, Vandoeuvre Les Nancy, France
  • 7Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, Bologna, Italy
  • 8Medical University of Warsaw, Wolska, Warsaw, Poland
  • 9Imperial College Healthcare NHS Trust, London, United Kingdom
  • 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. PROMISE was a randomised, double-blind, Phase III trial evaluating SMV plus peginterferon α-2a/ribavirin (PR) vs. placebo (PBO)/PR in genotype (GT)1 HCV patients who relapsed after previous interferon-based therapy. Efficacy and safety data from PROMISE are presented for European patients.

Methods: Patients received SMV 150 mg QD (12wks) with PR (24 or 48wks; based on response-guided therapy), or PBO (12wks) plus PR (48wks). Patients were stratified by HCV GT1 subtype and IL28B GT. Primary efficacy endpoint: sustained virological response at 12wks (SVR12).

Results: 274/393 (69.7%) patients were European (male 64.6%, white 97.8%, HCV GT1a/1b 29.2/70.4%, IL28B CC/CT/TT 22.6/65.3/12.0%, METAVIR F3/F4 14.7/14.0%); 18.5% of European HCV GT1a patients had Q80K. SVR12 was higher with SMV/PR versus PBO/PR in the European population overall and by patient sub-group. 173/184 SMV/PR patients (94.0%) were eligible for 24wks PR; 90.8% of these patients achieved SVR12. 81.5% of SMV/PR- and 3.4% of PBO/PR-treated patients achieved rapid virological response. On-treatment failure (3.3% vs. 20.0%) and viral relapse rates (11.9% vs. 43.5%) were lower with SMV/PR versus PBO/PR. In the SMV/PR arm (Wks1 – 12), most common AEs included fatigue, headache and influenza-like illness. Most were Grade 1/2 (Grade 3/4, 19.6%); no AEs resulted in SMV withdrawal. SAEs possibly related to SMV were infrequent (1.1%). No fatal AEs occurred.

Conclusion: SMV confers clinical benefit and is generally well tolerated in European HCV GT1-infected patients.

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