The study was sponsored by MSD

Transcription

1 A Phase 3, French Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve HCV GT1b-Infected Patients, with non-severe fibrosis : the STREAGER study A.Abergel 1, V. Loustaud-Ratti 2, V. Di Martino 3, J. Gournay 4, D. Larrey 5, I. Fouchard-Hubert 6, C. Hezode 7, T. Asselah 8, D. Samuel 9, B. Chanteranne 1, M. Dodel 1, F. Faure 1, B. Pereira 1, G. Lamblin 1, C. Campos 1, L. Muti 1, M. Reymond 1, C. Teilhet 1 1 Centre Hospitalier Universitaire de Clermont Ferrand, 2 Centre Hospitalier Universitaire de Limoges, 3 Centre Hospitalier Universitaire de Besançon, 4 Centre Hospitalier Universitaire de Nantes, 5 Centre Hospitalier Universitaire de Montpellier, 6 Centre Hospitalier Universitaire de Angers, 7 Centre Hospitalier Universitaire Henri Mondor (AP- HP), 8 Centre Hospitalier Universitaire Beaujon (AP-HP), 9 Centre Hospitalier Universitaire Paul Brousse (AP-HP)

2 Disclosures Abbvie: travel expenses and honoraria for teaching and board membership BMS: honoraria for teaching Gilead: travel expenses and honoraria for teaching and board membership MSD: travel expenses and honoraria for teaching and board membership The study was sponsored by MSD

3 Introduction Genotype 1b is the most common subtype of HCV infection, responsible for 22% of all infections world-wide Gower et al. J Hepatol. 2014;61:S45-S57

4 Adult viraemic patients infected by GT1b around the world North America (26%) 000 Europe North Africa/Middle East China Japan Latin America South Africa Australia Gower et al. J Hepatol. 2014;61:S45-S57

5 Adult viraemic patients infected by GT1b in Europe Western Europe : Central Europe : Eastern Europe : % 7% 17% 55% 71% 12% 30% 16% 50% 12% 33% 27% 52% 59% 88% 60% 54% 93% 40% 44% 58% 84% Gower et al. J Hepatol. 2014;61:S45-S57

6 Elbasvir and Grazoprevir HCV NS5A inhibitor, 50 mg HCV NS3/4A inhibitor, 100 mg Elbasvir (MK-8742) Grazoprevir (MK-5172) A once-daily, fixed-dose combination tablet for the treatment of patients with HCV GT1 or 4 infection 1 Broad activity versus most HCV genotypes in vitro 2-4 Efficacious in treatment-naive & treatment-experienced patients, cirrhotic and noncirrhotic patients, HIV/HCV co-infected patients and chronic kidney disease 5-7 Approved in Europe, US, Canada, and other countries worldwide 1. Zepatier [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; Summa V et al. Antimicrob Agents Chemother. 2012;56: Coburn CA et al. ChemMedChem. 2013;8: Harper S et al. ACS Med Chem Lett. 2012;3: Zeuzem S et al. Ann Intern Med. 2015;163: Rockstroh JK et al. Lancet HIV. 2015;2:e319-e Roth D et al. Lancet. 2015;38:

7 Grazoprevir/Elbasvir : SVR12 Genotype 1b in experienced (TE) and cirrhosis TN vs TE No cirrhosis vs cirrhosis SVR % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 97% EBR/GZR 12 weeks EBR/GZR 12 weeks % 90% 97% 97% 99.5% 80% 70% 60% 50% 40% 30% 20% 10% 0% EBR/GZR 12 weeks EBR/GZR 12 weeks TN TE No cirrhosis Cirrhosis Zeuzeum AASLD 2016, abs 874

8 Grazoprevir/Elbasvir +/- RBV: SVR12 genotype 1b naïve patients treated 8 weeks (C Worthy) 100% SVR12 ITT 75% 50% 92% (56/61) 96% (54/56) 25% 40% (2/5) 0% F0-F3 F0-F2 F3 Relapse Lost to follow-up Serfaty AASLD 2015, abs 701

9 Grazoprevir/Elbasvir +/- RBV: SVR12 genotype 1b naïve patients treated 8 weeks (C Worthy) SVR12 mitt 100% 75% 93% (56/60) 98% (54/55) 50% 25% 40% (2/5) 0% F0-F3 F0-F2 F3 Serfaty AASLD 2015, abs 701

10 Aim Evaluate the efficacy and safety of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis

11 Methods Inclusion criteria Patients were treatment-naïve, GT1b, without HIV/HBV co-infection Non severe fibrosis (F 2) was diagnosed according to a combination of two tests (J Boursier database, Angers) : Fibroscan lower than 9,5 kpa AND Fibrotest lower than 0.59

12 Study design Day 1 Week 8 Week 32 N = 120 ELB/GZR SVR 4 SVR 12 SVR 24

13 Demographics All patients N=74 Female, n (%) 48 (65) Age, mean (SD) 54 (12.6) BMI, mean (SD) 24.3 (3.9) ALAT > N, n (%) 30 (41) Baseline viral load, n (%) 800,000 IU/mL 28 (38) >800,000 IU/mL 46 (62) Fibrosis : Fibroscan (F0-F1 <7,1kPa), n (%) Fibrotest (F0-F1 <0,32), n (%) APRI < 1, n (%) FIB-4 < 1.45, n (%) FIB-4 < 2.5, n (%) 65 (88) 44 (59) 73 (99) 46 (62) 73 (99)

14 Results (1) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 97 % 72/74 SVR4 96 % 71/74 SVR12 Relapse 2 3 Lost-to-follow up (LTFU) 0 0

15 Results (2) Characteristics of the 3 relapsers BMI Kg/m2 ALT ULN Viral load IU/mL Fibrosis Score Patient kpa (F2) Patient kpa (F0-F1) Patient , kpa (F0-F1) Genotype at relapse 1e 1b 1b RAS at relapse L28M R30Q A92T Y93H Y93H L31M Y93H

16 Results (3) After exclusion of the patient with genotype 1e 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 99 % 72/73 SVR4 97 % 71/73 SVR12 Relapse 1 2 LTFU 0 0

17 Safety An 8-week regimen of EBR/GZR was well-tolerated with a favorable safety profile No adverse event grade 3 or 4 was observed The main adverse events with a frequency higher than 10% were: asthenia (26%) headache (23%) digestive disorders (14%)

18 Conclusions High cure rate (SVR12=97%) was achieved in a treatment-naïve non severe fibrosis GT1b-infected population treated by the combination of grazoprevir and elbasvir for 8 weeks Our results are in agreement with the results obtained in the C- Worthy study (SVR12=98%) in patients treated for 8 weeks These results are very similar to those obtained in patients treated for 12 weeks (SVR12=97%) These results are preliminary. Final study results on 120 patients to come next spring 2018

19 Thanks to : -the patients -all the investigators from the 14 centers Angers Beaujon Besançon Clermont Ferrand Cochin Henri Mondor Lille Limoges Lyon Montpellier Nantes Nice Paul Brousse Toulouse Isabelle Fouchart-Hubert Tarik Asselah Vincent Di Martino Armand Abergel Stanislas Pol Christophe Hézode Valérie Canva Véronique Loustaud-Ratti François Bailly Dominique Larrey Jérôme Gournay Albert Tran Didier Samuel Sophie Métivier

20 Kona in December Clermont Ferrand in December