Z Gastroenterol 2015; 53 - P56
DOI: 10.1055/s-0035-1551744

Shortening overall treatment to 12 weeks of Simeprevir (SMV) plus PEG-IFN/RBV in treatment-naïve chronic Hepatitis C (CHC) Genotype 1 patients: assessment of baseline and week 2 on-treatment predictors of SVR

M Gschwantler 1, T Asselah 2, C Moreno 3, C Sarrazin 4, GR Foster 5, A Craxi 6, P Buggisch 7, R Ryan 8, O Lenz 9, G Van Dooren 9, I Lonjon-Domanec 10, M Schlag 11, M Buti 12
  • 1Wilhelminenspital, Department of Internal Medicine IV, Vienna, Austria
  • 2Beaujon Hospital, University of Paris, Paris, France
  • 3CUB Hopital Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
  • 4Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
  • 5Queen Mary Hospital, University of London, Barts Health, London, United Kingdom
  • 6University of Palermo, Palermo, Italy
  • 7Institute for Interdisciplinary Medicine, Hamburg, Germany
  • 8Janssen Research & Development, Titusville, NJ, United States
  • 9Janssen Infectious Diseases BVBA, Beerse, Belgium
  • 10Janssen Pharmaceuticals, Paris, France
  • 11Janssen-Cilag, Vienna, Austria
  • 12Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain

Purpose: To assess whether Week-2 response with SMV+Peg-IFN/RBV can allow shortening treatment to 12 weeks, irrespective of baseline and on-treatment factors.

Design: Phase-3, open-label study in treatment-naïve CHC genotype 1-patients with no-to-moderate fibrosis (METAVIR F0-F2). In patients with HCV-RNA < 25 IU/mL (detectable/undetectable [Roche COBAS® Taqman® LLOQ: 25 IU/mL, LLOD: 15 IU/mL]) at Week 2 and undetectable at Weeks 4 and 8, all treatments were stopped at Week 12. If these criteria were not met, Peg-IFN/RBV was continued to Week 24. Concordance of response between Roche and Abbott RealTime assays was also determined.

Results: Of 163 patients treated, 123 (76%) fulfilled eligibility criteria for 12-week treatment (male: 53%, white: 92%, genotype 1a/b: 40/60%, METAVIR F0/1: 76%, IL28B CC/CT/TT: 26/59/15%). After SMV+Peg-IFN/RBV for 12 weeks, SVR12 was 65% (n = 123). Responses varied by baseline parameters and on-treatment response (Table 1).

One patient discontinued SMV and RBV (non-compliance). Treatment during the SMV+Peg-IFN/RBV phase was well tolerated (n = 163); 2.5% (n = 4) experienced a serious AE (none SMV related), 1.8% (n = 3) discontinued SMV+Peg-IFN/RBV due to an AE (1 possibly SMV-related [urinary incontinence]). Most frequent AEs were influenza-like illness 35.6%, pruritus 32%, fatigue 27%.

Conclusions: Week-2 response alone did not predict outcomes as baseline factors influenced SVR rates. High (> 80%) SVR12 rates were in: IL28B CC genotype patients, patients with low baseline viral load, or those with mild fibrosis (METAVIR F0/1) or GT1b and undetectable HCV RNA at Week 2.

Tab. 1: SVR12 for all patients and subgroups treated with 12 weeks SMV+Peg-IFN/RBV (ITT)

Treatment naïve (N = 123)

n/N (%)

Virologic response at Week 2*

< 25 IU/mL undetectable

39/51 (77)

< 25 IU/mL detectable

40/71 (56)

Overall

Week 2 undetectable

HCV genotype subtype

1a/other

30/49 (61)

13/19 (68)

1b

50/74 (68)

26/32 (81)

IL28B genotype

CC

30/32 (94)

12/13 (92)

CT

39/73 (53)

21/29 (72)

TT

11/18 (61)

6/9 (67)

Baseline HCV RNA IU/mL

≤800,000

27/33 (82)

16/20 (80)

> 800,000

53/90 (59)

23/31 (74)

METAVIR score

F0-F1

68/93 (73)

33/40 (83)

F2

11/29 (38)

5/10 (50)

SVR12 data was missing for 5 patients who were treated as not having achieved SVR.

* HCV RNA levels were measured using COBAS® TaqMan® HCV assay (v2.0; Roche)