Shortening overall treatment to 12 weeks of SIMEPREVIR plus pegylated-interferon/ribavirin according to early virologic response in treatment-naïve patients with chronic HCV genotype 4 infection and mild-to-moderate fibrosis

P Ferenci; T Asselah; C Moreno; A Craxi; F Sanai; R Ryan; O Lenz; G Van Dooren; I Lonjon-Domanec; M Schlag; M Buti

doi:10.1055/s-0035-1551766

Zeitschrift für Gastroenterologie, Table of Contents

Shortening overall treatment to 12 weeks of SIMEPREVIR plus pegylated-interferon/ribavirin according to early virologic response in treatment-naïve patients with chronic HCV genotype 4 infection and mild-to-moderate fibrosis

P Ferenci ¹, T Asselah ², C Moreno ³, A Craxi ⁴, F Sanai ⁵, R Ryan ⁶, O Lenz ⁷, G Van Dooren ⁷, I Lonjon-Domanec ⁸, M Schlag ⁹, M Buti ¹⁰

¹Medical University, Vienna, Austria
²Beaujon Hospital, University of Paris, Paris, France
³3CUB Hôpital Erasme Hospital, Université Libre de Bruxelles, Brüssel, Belgium
⁴University of Palermo, Palermo, Italy
⁵Division of Gastroenterology, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
⁶Janssen Research & Development, Titusville, NJ, United States
⁷Janssen Infectious Diseases BVBA, Beerse, Belgium
⁸Janssen Pharmaceuticals, Paris, France
⁹Janssen-Cilag, Vienna, Austria
¹⁰Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain

Abstract

Aims: HCV genotype 4 (GT4) is highly prevalent in the Middle East and Sub-Saharan Africa, and is expanding in Europe. To prevent disease progression, short and effective regimens are needed for these patients. This study aims to assess whether treatment with simeprevir+Peg-IFN/ribavirin can be shortened to 12 weeks, based on early viral kinetics, in patients with mild-to-moderate fibrosis.

Design: Phase-3, open-label study, including treatment-naïve patients in Europe and Saudi Arabia with HCV GT4. In patients with HCV-RNA < 25IU/mL (detectable/undetectable in IL28B CC, undetectable in CT/TT [Roche COBAS® Taqman®] at Week 2, and undetectable at Weeks 4 and 8, all treatments were stopped at Week 12. Otherwise, Peg-IFN/ribavirin was continued to Week 24. On-treatment and SVR4 data from the European patients are presented.

Results: 50 patients were enrolled (male: 72%, white: 83%, GT4a/d/other: 36/40/24%, METAVIR F0-F1/F2: 78/22%, IL28B non-CC: 84%). 46 patients completed simeprevir; three discontinued due to an AE; one met a virologic stopping rule. 24/50 were eligible for 12 weeks of treatment. 14/26 patients extending to 24 weeks are currently ongoing with Peg-IFN/ribavirin. Treatment with simeprevir+Peg-IFN/ribavirin was well tolerated: SAE (n = 1); grade 3/4 AE: 26%/0%.

Of the 24 patients eligible for 12 weeks (Table), none discontinued or relapsed to date. Among initial patients evaluable, SVR4 was 94% (16/17; one patient missing SVR4 data).

*Tab. 1:* Patient eligibility for 12- or 24-week planned treatment duration, by subgroups
	n/N (%)
Total
Met 12-week criteria	24/50 (48)
Did not meet 12-week criteria	24/50 (48)
Not classifiable	2/50 (4)
GT4a
Met 12-week criteria	8/18 (44)
Did not meet 12-week criteria	9/18 (50)
Not classifiable	1/18 (6)
GT4 d
Met 12-week criteria	10/20 (50)
Did not meet 12-week criteria	9/20 (45)
Not classifiable	1/20 (5)
GT4 other
Met 12-week criteria	6/12 (50)
Did not meet 12-week criteria	6/12 (50)
IL28B CC
Met 12-week criteria	8/8 (100)
IL28B CT
Met 12-week criteria	12/33 (36)
Did not meet 12-week criteria	19/33 (58)
Not classifiable	2/33 (6)
IL28B TT
Met 12-week criteria	4/9 (44)
Did not meet 12-week criteria	5/9 (56)

Conclusions: 48% of GT4 patients met the criteria for stopping treatment at Week 12. Of these patients, preliminary SVR4 rates are promising in GT4a/d, with SVR12/24 data and SVR data in Saudi Arabian patients forthcoming.