GS-US Study: SOF/VEL + GS-9857 in genotype 1 - Phase II

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Presentation transcript:

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Design Open-label W6 W8 W12 N = 34 SOF/VEL + GS-9857 > 18 years Genotype 1 HCV RNA > 10 000 IU/ml Treatment-naive or treatment-experienced (NS5A inhibitor or ≥ 2 DAA classes experienced) Compensated cirrhosis allowed Creatinine clearance > 60 ml/min No HBV or HIV co-infection No cirrhosis Naive N = 36 SOF/VEL + GS-9857 N = 33 SOF/VEL + GS-9857 Cirrhosis Naive N = 31 SOF/VEL + GS-9857 + RBV N = 31 DAA- experienced SOF/VEL + GS-9857 N = 32 SOF/VEL + GS-9857 + RBV SOF/VEL: 400/100 mg FDC qd ; GS-9857: 100 mg qd RBV: 1000 or 1200 mg/day in 2 doses according to weight (< or ≥ 75 kg) Objective SVR12 (HCV RNA < 15 IU/ml), by ITT, with 2-sided 95% CI (no inferential statistics) GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Baseline characteristics Naive DAA-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 34 8W N = 36 N = 33 SOF/VEL + GS-9857 + RBV N = 31 12W N = 32 Age, years, mean 53 51 58 59 57 Female, % 32 42 39 26 19 White, % 91 89 76 84 87 81 HCV RNA, log10 IU/ml 6.2 6.0 6.3 6.4 IL28B CC, % 35 25 21 13 Genotype 1a / 1b, % 79 / 21 78 / 22 81 / 19 87 / 13 75 / 25 DAA experience, N LDV DCV Other NS5A NS3A + NS5B - 5 5 7 14 2 6 4 20 GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II SVR12, ITT, % (95% CI) DAA-experienced 20 40 60 80 100 71 ( 53-85) 34 (89-100) 33 31 % N= 94 (80-99) 81 (63-93) (94-100) 32 Naive without cirrhosis ( 90-100) 36 Naive with cirrhosis No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W 8W + RBV 12W GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Resistance analysis (1% deep sequencing) At baseline, presence of class RASs (NS3, NS5A or NS5B) 81/134 (60%) treatment-naïve patients 51/63 (81%) DDA-experienced patients 93% if NS5A-experienced vs 18% if not NS5A-experienced In treatment-naïve patients, 8 weeks of SOF/VEL + GS-9857 led to SVR12 in 96% (25/26) and 97% (42/43) of patients without and with baseline RASs, respectively All DAA-experienced patients, regardless of the presence of single or multi-class RASs, achieved SVR12 following 12 weeks of SOF/VEL + GS-9857 At relapse (sequencing data in 17/18): 10/17 (59%) had the same number or fewer RASs at the time of virologic relapse than at baseline 4/17(24%) had no RASs both at baseline and at virologic relapse Only 3 patients had treatment-emergent RASs, all in the NS3 gene and all at frequencies less than 2% of the viral population: V170T, Q41R + A156T, V36M GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Adverse events, % Naive DAA-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 34 8W N = 36 N = 33 SOF/VEL + GS-9857 + RBV N = 31 12W N = 32 AE leading to discontinuation 3 Death AE in ≥ 5% of patients Headache Nausea Fatigue Diarrhea Insomnia Constipation Nasopharyngitis Anemia Cough Dizziness 32 6 12 15 19 28 17 11 8 21 9 26 29 29 10 10 3 13 10 23 16 9 9 9 0 0 0 0 3 GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Laboratory abnormalities, N (%) Naive DAA-experienced No cirrhosis Cirrhosis SOF/VEL + GS-9857 6W N = 34 8W N = 36 N = 33 SOF/VEL + GS-9857 + RBV N = 31 12W N = 32 Hemoglobin < 10 g/dl 4 (13) Platelets 25-50 000/mm3 1 (3) 2 (6) INR 2-3 x ULN NR ALT 5-10 x ULN CK 10-20 x ULN Glycemia 2.5-5 g/l Lipase > 5 x ULN 4 (12) Bilirubin 2.5-5 x ULN 3 (10) 1(3) GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901

GS-US-367-1168 Study: SOF/VEL + GS-9857 in genotype 1 - Phase II Summary In this phase 2 open-label trial, 8 weeks treatment with SOF/VEL + GS-9857 was safe and effective in treatment-naïve patients ; 12 weeks was safe and effective in patients previously treated with DAAs The combination was safe and effective in patients with or without compensated cirrhosis GS-US-367-1168 Lawitz E, Gastroenterology 2016; 151:893-901