TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 ARV-trial.com TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 Design No randomisation Open-label W12 W24 GT1a, no cirrhosis OBV/PTV/r + DSV + RBV SVR12 > 18 years HCV infection, genotype 1 HCV RNA > 1,000 IU/ml Naïve or pre-treated with IFN or PEG-IFN + RBV With or without compensated cirrhosis GT1a, cirrhosis OBV/PTV/r + DSV + RBV SVR12 GT1b, no cirrhosis OBV/PTV/r + DSV SVR12 GT1b, cirrhosis OBV/PTV/r + DSV + RBV SVR12 Treatment regimens Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r): 25/150/100 mg qd = 2 tablets Dasabuvir (DSV): 250 mg bid RBV: 1 000 or 1 200 mg/day in 2 doses according to body weight (< or > 75 kg) Objective SVR12 (HCV RNA <15 IU/ml), with 95% CI, by ITT, descriptive analysis TOPAZ-II Neau R. AASLD 2015, Abs. 1065 1
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 ARV-trial.com TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 Baseline characteristics OBV/PTV/r + DSV + RBV N = 615 Mean age, years 55 Female 36% White / Black 85% / 14% Genotype 1a / 1b, n 451 / 163 HCV RNA, log10 IU/ml, mean 6.0 Fibrosis stage : F0-F1/ F2 / F3 / F4 49% / 14% / 18% / 19% IL28B CC genotype 24% Naïve 71% Prior treatment with IFN or PEG-IFN + RBV Intolerant Non response Breakthrough/relapse 29% 21% 45% 34% TOPAZ-II Neau R. AASLD 2015, Abs. 1065 2
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 SVR12, % (ITT) % 96 98 98 97 96 96 96 100 95 93 95 95 95 92 80 60 40 20 615 437 178 452 163 134 481 146 467 304 88 108 115 Naïve Experienced GT1a GT1b <800 000 >800 000 CC Non-CC F0-F1 F2 F3 F4 Overall ITT Prior treatment experience Genotype HCV RNA IU/ml IL28B genotype Fibrosis stage TOPAZ-II Neau R. AASLD 2015, Abs. 1065
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 SVR12, % (mITT*) 20 40 60 80 100 97 98 95 99 96 602 428 174 Naïve Experienced GT1a GT1b <800 000 >800 000 CC Non-CC F0-F1 F3 F4 IL28B genotype Fibrosis stage HCV RNA IU/m Genotype Prior treatment experience Overall ITT 441 161 131 471 144 456 297 87 107 111 F2 % * Sensitivity analysis excluding excluding patients lost to follow-up and patients that prematurely discontinued study drug with no on-treatment virologic failure TOPAZ-II Neau R. AASLD 2015, Abs. 1065
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 Patients not achieving SVR12 (ITT population) Reasons for non-response n/N (%) Virologic failure 16/615 (2.6%) Breakthrough 5/615 (0.8%) Relapse (by post-treatment W12) 11/590 (1.9%) Premature discontinuation* 3/615 (0.5%) Missing SVR12 data 10/615 (1.6%) *2 patients discontinued due to an adverse event ; 1 patient withdrew consent TOPAZ-II Neau R. AASLD 2015, Abs. 1065
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 ARV-trial.com TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 Treatment emerging adverse events and laboratory abnormalities, N (%) OBV/PTV/r + DSV + RBV, N = 615 Serious adverse event 4% Discontinuation for adverse event 6 (1%) ** Adverse event leading to RBV dose reduction 73 (12%) Fatal adverse event 1 (0.2%) ** Adverse event in ≥ 10% of patients Fatigue 32% Nausea 16% Headache Pruritus 13% Insomnia Hemoglobin Grade 2 : 8-10 g/dl Grade 3 : 6.5-8 g/dl 6% 0.3% ALT : grade 3 (5-20 x ULN) / grade 4 (> 20 x ULN) 4 (0.7%) / 1 (0.2%) AST : grade 3 (5-20 x ULN) / grade 4 3 (0.5%) / 0 Total bilirubin : grade 3 (3-10 x ULN) / grade 4 3% / 0.2% * Nausea (N = 2), fatigue (N = 1), lethargy/vomiting (N = 1), hypercortisolism (N = 1), peritonitis (N = 1) ** Death due to metastatic pancreatic adenocarcinoma (Stage IV). Unrelated to HCV therapy TOPAZ-II Neau R. AASLD 2015, Abs. 1065 6
TOPAZ-II Study: OBV/PTV/r + DSV + RBV for genotype 1 Summary In the TOPAZ-II study, treatment-naïve or -experienced patients with HCV genotype 1 infection with or without cirrhosis achieved high SVR12 rates (95.3% in the ITT population and 97.3% in the mITT population) with 12- or 24-weeks of treatment with OBV/PTV/r + DSV ± RBV Treatment was well tolerated with low rates of serious adverse events and study drug discontinuations due to adverse events TOPAZ-II Neau R. AASLD 2015, Abs. 1065