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Failure to achieve SVR on No HBV or HIV co-infection

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Presentation on theme: "Failure to achieve SVR on No HBV or HIV co-infection"— Presentation transcript:

1 Failure to achieve SVR on No HBV or HIV co-infection
ARV-trial.com GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA Design Open-label W12 Chronic HCV infection Genotype 1 Failure to achieve SVR on GS-9451* or GS-9256*- containing regimen No HBV or HIV co-infection N = 80 SOF + PEG-IFN + RBV SVR12 * GS-9451 (vedroprevir) : 1st generation PI ; GS-9256 : 1st generation PI SOF 400 mg : 1 pill qd PEG-IFNa-2a 180 mg SC once weekly RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Objective Primary endpoint : SVR12 (HCV RNA < 25 IU/ml) by intention to treat, with 2-sided 95% CI, no statistical hypothesis GS-9451/9256 Failure Pol S. Hepatology 2015; 62:129-34 1

2 Baseline characteristics
ARV-trial.com GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA Baseline characteristics N = 80 Mean age, years 55 Female 25% White / Black 82% / 14% IL28B CC genotype 16% HCV RNA log10 IU/ml, mean 6.6 Cirrhosis Genotype 1a / 1b 85% / 15% Previous treatment experience < 12W / ≥ 12W PEG-IFN + RBV GS-9451/9256 GS-9451/ LDV GS LDV GS TGV + LDV 27.5% / 72.5% 99% (79/80) 8% 13% 53% 28% Baseline RAVs NS3 NS5A SOF 74/79 38 (51%) 66 (84%) 3 (4%) GS-9451/9256 Failure Pol S. Hepatology 2015; 62:129-34 2

3 ARV-trial.com GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA Outcome N = 80 SVR12, N (% [95% CI]) 63 (79% [68-87) Relapse 17 (21%) SVR12 by subgroup n/N Male Female 47/60 16/20 78% 80% Black Non-black 7/11 58/69 64% 81% Genotype 1a Genotype 1b 54/68 9/12 79% 75% Baseline HCV RNA, log 10 IU/ml < 6 ≥ 6 7/8 56/72 89% IL28B genotype CC Non-CC 13/13 49/66 100% 74% Baseline SOF RAVs 2/3 67% Emergence of NS5B RAV at relapse : 1 patient with emergence of L159F and 1 with emergence of S282G ; no emergence of S282T GS-9451/9256 Failure Pol S. Hepatology 2015; 62:129-34 3

4 ARV-trial.com GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA Adverse events Serious adverse event : 1 (dysphagia, unrelated) Discontinuation due to adverse event : 3 (PEG-IFN in 2, RBV in 1) Most common adverse events : Fatigue (43%) Headache (35%) Nausea (24%) Neutropenia (23%) Influenza-like illness (19%) Myalgia (15%) Pruritus (15%) Rash (15%) Grade 3 / grade 4 laboratory abnormalities : 41% / 10% Mean decrease in hemoglobin : -2.8 g/dl GS-9451/9256 Failure Pol S. Hepatology 2015; 62:129-34 4

5 ARV-trial.com GS-9451/GS-9256 Failure Study: SOF + PEG-IFN + RBV for genotype 1 and prior failure to DAA Summary In this open-label study, 12 weeks of treatment with SOF + PEG-IFN + RBV resulted in a high rate of SVR12 in patients without cirrhosis who had not achieved SVR in previous trials involving PEG-IFN/RBV plus a protease inhibitor with and without other DAAs Similar SVR12 by baseline patient characteristics High efficacy regardless of baseline RAVs : benefit of using a different class (SOF) Limitations Small sample size Uncontrolled design Lack of patients with cirrhosis GS-9451/9256 Failure Pol S. Hepatology 2015; 62:129-34 5

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