COMMIT Study: SMV + DCV in genotype 1b

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Presentation transcript:

COMMIT Study: SMV + DCV in genotype 1b Design Open-label W12-24* > 18 years Genotype 1b Treatment-naïve HCV RNA ≥ 10 000 IU/ml Advanced fibrosis or compensated cirrhosis (F3/F4) No baseline NS5A-Y93H and/or L31M/V (pop. Sequencing) N = 106 SMV 150 mg qd + DCV 60 mg qd * 12 weeks in the first 17 patients ; due to observations of breakthrough, next 89 patients treated for 12 or 24 weeks based on patient wish and investigator discretion Objective SVR12 (HCV RNA < 15 IU/ml), with 95% CI, by ITT COMMIT Hezode C, Liver International 2017 ; 37:1304-13

COMMIT Study: SMV + DCV in genotype 1b Baseline characteristics 12 weeks 1st cohort N = 17 2nd cohort N = 25 24 weeks N = 64 Median age, years 53 64 59 Female 29% 44% 42% Caucasian 100% 97% Median BMI, kg/m² 24.2 25.4 25.0 Median HCV RNA, log10 IU/ml 6.45 6.19 6.21 IL28B CC 18% 28% 32% Metavir F3 / F4 * 76% / 24% 80% / 20% 50% / 50% Diabetes 12% 8% 17% Arterial hypertension 47% 33% Median eGFR, ml/min 95.5 80.3 89.9 * Significantly more patients with cirrhosis received 24 weeks of treatment COMMIT Hezode C, Liver International 2017 ; 37:1304-13

COMMIT Study: SMV + DCV in genotype 1b SVR12, % (ITT) 20 40 60 80 100 71 17 12W 1st cohort 25 64 94 89 96 Baseline HCV RNA (IU/ml) 30 IL28B genotype % 95 86 85 53 22 65 41 2nd cohort 24W < 4 000 000 ≥ 4 000 000 CC CT TT Metavir Score F3 F4 COMMIT Hezode C, Liver International 2017 ; 37:1304-13

COMMIT Study: SMV + DCV in genotype 1b Treatment failure, N = 9 12 weeks 1st cohort N = 17 2nd cohort N = 25 24 weeks N = 64 On-treatment failure Viral breakthrough Consent withdrawal 5 4 1 3 Relapse Viral breakthrough, N = 7 Baseline HCV RNA (x 106 IU/ml) IL28B Metavir Time of failure Baseline SMV RAVs / NS5A RAVs Time of failure SMV RAVs / NS5A RAVs Male 8.2 TT F3 W4 None / None D168E / L31V, Y93H Female 22.7 CT F4 D168V / P32 deletion 4.7 2.6 W8 D168V / L31V, Y93H 6.8 F2 W12 2.1 None / R30Q D168V / L31M, Q54H, Q62E, Y93H 5.6 W16 D168V / L31V, Q54H, Y93H COMMIT Hezode C, Liver International 2017 ; 37:1304-13

COMMIT Study: SMV + DCV in genotype 1b Adverse events, % All patients Any adverse event 70 Grade 3-4 AE 7 Serious AE 6 Possibly related to SMV 1 (N = 1, photosensitivity) Possibly related to DCV Treatment-related AE 47 44 Discontinuation due to AE 3 (N = 3, grade 4 amylase, pericarditis on amiodarone, acute kidney injury) COMMIT Hezode C, Liver International 2017 ; 37:1304-13

COMMIT Study: SMV + DCV in genotype 1b Summary SMV + DCV demonstrated efficacy in treatment-naïve HCV genotype 1b infected patients with advanced fibrosis or compensated cirrhosis (F3 or F4) SVR12 was 92% Viral breakthrough was observed in 6.6% of patients (4/17 of those treated for 12 weeks), in the absence of baseline RAVs Emerging SMV and DCV RAVs were detected at time of failure in all patients with viral breakthrough The combination was well tolerated 3% of patients discontinued treatment due to adverse events In conclusion, SMV + DCV is not an optimal regimen High SVR12 rate But viral breakthrough not predictable (not related to PK, nor pre-existing RAVs at baseline) COMMIT Hezode C, Liver International 2017 ; 37:1304-13