SOF/VEL + GS-9857 in genotypes 1-6 Phase II Design W6 W8 No randomisation Open-label SOF/VEL + GS-9857 SVR12 > 18 years Chronic HCV infection Genotype 1 to 6 Naïve Compensated cirrhosis allowed No HBV or HIV co-infection Genotype 1-6 N = 166 SOF/VEL + GS-9857 SVR12 Genotype 1, cirrhosis SOF/VEL + GS-9857 + RBV SVR12 N = 31 SOF/VEL: 400/100 mg qd GS-9857: 100 mg qd Objective SVR12 (HCV RNA < 15 IU/ml), by ITT SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II Baseline characteristics and patient disposition SOF/VEL + GS-9857 6 weeks N = 67 8 weeks N = 99 SOF/VEL + GS-9857 + RBV N = 31 Age, years, mean 53 55 59 Female 48% 38% 39% White 87% 82% 84% HCV RNA, log10 IU/ml, mean 6.2 6.1 6.3 IL28B CC 34% 27% Cirrhosis 64% 100% Genotype : 1 / 2 / 3 / 4 / 5 / 6 52% / 9 % / 31% / 7% / 0 / 0 70% / 6% / 18% 5% / 0 / 1% 100% / 0 / 0 0 / 0 / 0 Discontinuation due to adverse event 2 1 SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II SVR12 by genotype, and by cirrhosis SOF/VEL + GS-9857 6W SOF/VEL + GS-9857 8W SOF/VEL + GS-9857 + RBV 8W % 100 100 96 94 81 79 81 80 71 60 40 20 N= 67 99 31 35 36 33 31 Genotype 1-6 Genotype 1 No cirrhosis Genotype 1 Cirrhosis Genotype 1 SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II SVR12 in genotype 2, 3, 4, 6 by genotype and cirrhosis SOF/VEL + GS-9857 6W SOF/VEL + GS-9857 8W % 100 100 93 94 100 88 83 80 67 60 60 40 20 N= 67 99 31 15 15 16 4 4 Overall Genotype 2 Genotype 3 Genotype 4 Overall Genotype 2 Genotype 3 Genotype 4, 6 SOF/VEL + GS-9857 6W No cirrhosis SOF/VEL + GS-9857 8W Cirrhosis SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II SVR12 according to presence of baseline RAVs (deep sequencing with 15% threshold) SOF/VEL + GS-9857 6W SOF/VEL + GS-9857 8W SOF/VEL + GS-9857 + RBV 8W Baseline RAVs No : 53% 32/39 (82%) 49/51 (96%) 12/14 (86%) Yes : 47% 21/28 (75%) 46/48 (96%) 13/17 (77%) RAVs at virologic failure (sequencing in 23/24 relapses) No treatment-emergent RAVs SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II Adverse events and laboratory abnormalities % SOF/VEL + GS-9857 6W SOF/VEL + GS-9857 8W SOF/VEL + GS-9857 + RBV 8W Any adverse event 66% 69% 81% Grade 3-4 adverse event 1% 2% Serious adverse event Discontinuation for adverse event * 3% Adverse events in ≥ 10% of patients Headache 31% 17% 26% Nausea 16% 20% 29% Fatigue 11% DIarrhea 21% 9% 10% Anemia 19% Grade 3-4 laboratory abnormalities 4% 35% * ALT/AST elevations (N = 1) at W2, which returned to baseline values after stopping treatment ; diarrhea, nausea and vomiting (N = 1) ; fatigue (N = 1) SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758
SOF/VEL + GS-9857 in genotypes 1-6 Phase II Summary SOF/VEL + GS-9857 once daily for 8 weeks was highly effective in treatment-naïve, genotype 1-6 patients with and without cirrhosis Overall SVR12 was 96% In genotype 1, SVR12 was 100% if no cirrhosis, 94% if cirrhosis In genotype 2-6, SVR12 was 88% if no cirrhosis, 93% if cirrhosis Addition of RBV did not improve SVR12 in genotype 1 patients treated for 8 weeks, actually even lower 6 week treatment was associated with high relapse rate Presence of baseline RAVs had no impact on SVR12 rate in patients with genotype 1 treated for 8 weeks Treatment was generally well tolerated SOF/VEL + GS-9857 naïve - Phase II Gane EJ, EASL 2016, Abs. SAT-138, J Hepatol 2016; 64:S758