Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE

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Presentation transcript:

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Phase 2 Treatment Experienced Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE (1) Buti M, et al. Clin Infect Dis. 2016;62:32-6. (2) Forns X, et al. J Hepatol. 2015;63:564-72.

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Features C-SALVAGE Trial Design: Prospective, open-label, single-arm, phase 2 trial examining the safety and efficacy of elbasvir plus grazoprevir plus ribavirin for 12 weeks in treatment-experienced patients with GT 1 HCV, with or without cirrhosis, and previous failure of peginterferon and ribavirin plus an early-generation HCV protease inhibitor (boceprevir, simeprevir, or telaprevir) Entry Criteria - Chronic HCV Genotype 1 - 18 years or older - HCV RNA ≥10,000 IU/mL - Prior treatment failure with ≥4 weeks of peginterferon + ribavirin + PI - Patients with compensated cirrhosis accepted Primary End-Points: SVR12 data analysis: Buti M, et al. Clin Infect Dis. 2016;62:32-6. SVR24 data analysis: Forns X, et al. J Hepatol. 2015;63:564-72. Source: (1) Buti M, et al. Clin Infect Dis. 2016;62:32-6. (2) Forns X, et al. J Hepatol. 2015;63:564-72.

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Design Week 12 24 PI+PR experienced Genotype 1 Non-cirrhotic (N=45) Cirrhotic (N=34) EBR + GZR + RBV N=79 SVR12 Abbreviations: EBR = elbasvir; GZR = grazoprevir; RBV = ribavirin; PI = protease inhibitor; PR = peginterferon+ribavirin Drug Dosing: Elbasvir: 50 mg once daily Grazoprevir: 100 mg once daily Ribavirin (weight-based and divided bid): 800 to 1400 mg/day Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Participants Baseline Characteristic All Patients (N=79) Baseline NS3 RAVs* (N=34) No Baseline NS3 RAVs* (N=44) Mean age, years 54.4 53.9 54.6 Male/Female, % 58.2/41.8 61.8/38.2 54.5/45.5 HCV genotype, % 1a 1b 38.0 62.0 67.6 32.4 15.9 84.1 Cirrhosis, % 43.0 44.1 43.2 Previous PI, % Boceprevir Telaprevir Simeprevir 35.4 10.1 29.4 55.9 14.7 38.6 54.5 6.8 Non-virologic failure+, % 16.5 5.9 25.0 * Among evaluable patients + Reasons for the 13 non-virologic failure included adverse events/drug intolerance (n=12) and short course regimen in a clinical trial (n=1) Source: Forns X, et al. J Hepatol. 2015;63:564-72.

C-SALVAGE: SVR 24* by Baseline Factors Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Results C-SALVAGE: SVR 24* by Baseline Factors 76/79 63/66 33/36 32/34 * Analysis per protocol: excluding patients who dropped out due to reasons other than virologic failure RAVs = resistance-associated variants (at baseline) Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

SVR24 in Patients with Baseline RAVs Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Results SVR24 Related to Baseline RAVs in 79 Patients with Prior Virologic Failure Categories of RAVs Baseline RAV SVR24 in Patients with Baseline RAVs NS3 RAV 34/79 (43%) 31/34 (91%) NS5A RAV 9/79 (11%) 8/9 (89%) Total 43/79 (54%) 39/43 (91%) RAV = Resistance Associated Variants Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.

Grazoprevir + Elbasvir + Ribavirin Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Adverse Events Adverse Event (AE), n (%) Grazoprevir + Elbasvir + Ribavirin (N=79) Discontinuation due to AE 1 (1.3%) Serious AEs 4 (5.1%) Deaths Specific AE in ≥10% of patients Fatigue Headache Asthenia Nausea 22 (28%) 15 (19%) 12 (15%) 9 (12%) Grade 3 or 4 laboratory abnormality Total bilirubin Direct bilirubin AST or ALT Lipase Hemoglobin Grade 3 2 (2.5%) Grade 4 Source: Forns X, et al. J Hepatol. 2015;63:564-72.

Elbasvir + Grazoprevir + Ribavirin in PI-experienced HCV GT1 C-SALVAGE Study: Conclusions Conclusions: “Grazoprevir and elbasvir with ribavirin for 12 weeks maintained HCV suppression for at least 24 weeks posttherapy without late relapses. Baseline resistance-associated variants (RAVs) stably reappeared at relapse in all 3 patients with virologic failure. NS5A RAVs emerging at relapse persisted for the full 24-week follow-up period. If confirmed, this finding could complicate retreatment of the small number of patients failing regimens containing an NS5A inhibitor.” Source: Buti M, et al. Clin Infect Dis. 2016;62:32-6.