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Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label 18-65 years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I)

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Presentation on theme: "Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label 18-65 years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I)"— Presentation transcript:

1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE TVR + PEG-IFN + RBV Randomisation Open-label 18-65 years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve (MALACHITE-I) Failure to prior PEG-IFN + RBV (MALACHITE-II) No cirrhosis No HBV or HIV co-infection MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1  Design N = 69 W12W48 * Randomisation was stratified on IL28B (CC or non-CC) PEG-IFN + RBV OPV/PTV/r + DSV + RBV PEG-IFN + RBV TVR + PEG-IFN + RBV PEG-IFN + RBV OPV/PTV/r + DSV + RBV PEG-IFN + RBV OPV/PTV/r + DSV TVR + PEG-IFN + RBV PEG-IFN + RBV OPV/PTV/r + DSV + RBV PEG-IFN + RBV GT1a naïve GT1b naïve * ** * Experienced ** Randomisation was stratified on genotype (1a or 1b) and previous response to PEG-IFN + RBV (null response, partial response, relapse) W24 N = 34 N = 84 N = 83 N = 101 N = 47 N = 41

2  Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r): 25/150/100 mg qd = 2 tablets –Dasabuvir (DSB) : 250 mg bid –TVR: 750 mg tid, 8h apart –PEG-IFN  -2a : 180  g SC once weekly –RBV: 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) –In TVR groups, additional 12 or 36 weeks of PEG-IFN + RBV depended on virologic response at treatment W4-12  Primary efficacy endpoint –MALACHITE-I: Non inferiority of OBV/PTV/r + DSB + RBV compared to TVR + PEG-IFN + RBV in genotype 1a and of OBV/PTV/r + DSB compared to TVR + PEG-IFN + RBV in genotype 1b: SVR 12 (HCV RNA < 25 IU/ml) by intention to treat (lower margin of the 2-sided 95% CI for the difference with TVR = - 10.5%) –MALACHITE-II: % of patients achieving SVR 12 between treatment arms using a logistic regression model with treatment arm, baseline log 10 HCV RNA level, HCV subgenotype (1a, non-1a), and previous PEG-IFN + RBV treatment response (relapse, partial response, null response) MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE

3 Genotype 1aGenotype 1b OBV/PTV/r + DSV + RBV N = 69 TVR + PEG-IFN + RBV N = 34 * OBV/PTV/r + DSV + RBV N = 84 OBV/PTV/r + DSV N = 83 TVR + PEG-IFN + RBV N = 41 * Mean age, years4645464746 Female30%50%55%52%59% White90%88%95%99%93% IL28B CC genotype 28%32%17% HCV RNA log 10 IU/ml, mean6.296.376.366.336.23 Metavir fibrosis score F0-F1 / F2 / ≥ F3 72% / 18% / 10% 71% / 21% / 9% 83% / 8% / 8% 72% / 13% / 14% 76% / 10% / 15% Discontinued treatment, N Virologic failure Adverse event Withdrawal Other 2110121101 6121261212 009541195411 Baseline characteristics and patient disposition (MALACHITE-I, treatment-naïve) MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 * Among the 75 patients in the TVR groups, 59 received 24 weeks of PEG-IFN + RBV, 16 received 48 weeks Dore G. J Hepatol 2016; 64:19-28 MALACHITE

4 OBV/PTV/r + DSV + RBV N = 101 TVR + PEG-IFN + RBV N = 47 Mean age, years4745 Female46%40% White100% Genotype 1a / 1b19% / 81%15% / 85% IL28B CC genotype 8%13% HCV RNA log 10 IU/ml, mean6.376.39 Metavir fibrosis score F0-F1 / F2 / ≥ F378% / 17% / 5%68% / 23% / 9% Response to prior PEG-IFN + RBV : Relapse / Partial response / Null response 27% / 25% / 49%26% / 26% / 49% Duration of PEG-IFN + RBV : 24W / 48W, N- 10 (prior relapse) / 37 (null-partial response) Discontinued treatment, N Virologic failure Adverse event Withdrawal 0 15 9 5 2 Baseline characteristics and patient disposition (MALACHITE-II, Treatment-experienced) MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE

5 SVR 12 (HCV RNA < 25 IU/ml), % (95% CI) On treatment failure2*20*1509 Relapse001**0202 Failure to achieve SVR 12 for other reasons *** 0401215 Genotype 1a: non-inferiority of OBV/PTV/r + DSV + RBV to TVR + PEG-IFN + RBV Genotype 1b: non-inferiority and superiority of OBV/PTV/r + DSV and of OBV/PTV/r + DSV + RBV to TVR + PEG-IFN + RBV ** Reinfection (Genotype 2a) *** Missing data or premature discontinuation * These 3 patients were adherent. At the time of failure, detection of resistance variants at in NS3, NS5A, and/or NS5B that were not present at baseline MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE % N6941348447 97 (93-100) 99 (97-100) 99 (97-100) 82 (68-96) 98 (94-100) 66 (53-79) 0 20 40 60 80 100 Genotype 1bAll patients 83 OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV TVR + PEG-IFN + RBV Genotype 1a MALACHITE-I (treatment-naïve) MALACHITE-II (treatment-experienced) 78 (66-91) 101

6 MALACHITE-IMALACHITE-II OBV/PTV/r + DSV + RBV N = 153 OBV/PTV/r + DSV N = 83 TVR + PEG- IFN + RBV N = 75 OBV/PTV/r + DSV + RBV N = 101 TVR + PEG- IFN + RBV N = 47 Serious adverse event, N10915 AE leading to discontinuation1 *0605 AE occurring in ≥ 5% in non IFN-groups Headache27%19%31%29%45% Nausea21%8%40%10%43% Pruritus 12%6%35%13%40% Fatigue14%5%31%12%26% Anemia7%1%45%3%34% Rash8%023%3%26% Asthenia7%2%20%8%34% Cough7%1%12%7%26% Insomnia9%0 6%21% Adverse events MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 * Hot flush and fatigue Dore G. J Hepatol 2016; 64:19-28 MALACHITE

7 MALACHITE-IMALACHITE-II OBV/PTV/r + DSV + RBV N = 153 OBV/PTV/r + DSV N = 83 TVR + PEG- IFN + RBV N = 75 OBV/PTV/r + DSV + RBV N = 101 TVR + PEG- IFN + RBV N = 47 Hemoglobin, g/dl 8 to < 101%043%4%26% < 81%04%09% ALT > 5 x ULN1%00 6% AST > 5 x ULN 1% 0 2% Total bilirubin > 3 x ULN4%03%1%2% Laboratory abnormalities, % Patient-reported outcomes  SF-36v2 self-administered questionnaire: overall, the difference between the 2 regimens in the changes from baseline in Mental Component Summary and Physical Component Summary throughout the treatment and post-treatment periods in both treatment-naïve and treatment-experienced patients favored the OBV/PTV/r + DSV + RBV regimen MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE

8  Summary –This is the first head-to-head study of an all-oral, DAA (OBV/PTV/r + DSV + RBV) and a PEG-IFN-containing (TVR + PEG-IFN + RBV) regimen that quantitatively compares efficacy and safety benefits in treatment-naïve and treatment-experienced HCV genotype 1-infected patients –SVR 12 rate was numerically higher with OBV/PTV/r + DSV + RBV (97-99%) than with TVR + PEG-IFN + RBV (66-82%) regardless of subgenotype or prior treatment status –Better tolerability of OBV/PTV/r + DSV + RBV –Higher improvement in mental and physical health in patients receiving OBV/PTV/r + DSV + RBV –Limitations Exclusion of cirrhosis Absence of black patients Low number of experienced patients with genotype 1a MALACHITE study: OBV/PTV/r + DSV + RBV versus telaprevir + PEG-IFN + RBV in genotype 1 Dore G. J Hepatol 2016; 64:19-28 MALACHITE

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