SMV + PEG-IFN + RBV Open-label W12 W24* or W48* N = 107 18-70 years Chronic HCV infection Genotype 4 Treatment-naïve or experienced with relapse or partial.

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No HBV or HIV co-infection

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Presentation transcript:

SMV + PEG-IFN + RBV Open-label W12 W24* or W48* N = years Chronic HCV infection Genotype 4 Treatment-naïve or experienced with relapse or partial or null response to PEG-IFN + RBV HCV RNA ≥ 10,000 IU/ml No HBV or HIV co-infection –SMV : 150 mg qd ; PEG-IFN  -2a : 180  g SC once weekly –RBV weight based (bid dosing) : 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg PEG-IFN + RBV * Treatment-naïve and relapsers stopped therapy at W24 if HCV RNA < 25 IU/ml at W4 and HCV RNA undetectable at W12 ; All other patients continued therapy until W48 RESTORE Moreno C. J Hepatol 2015;62: RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4  Objective –SVR 12 (HCV RNA < 25 IU/ml) with 95% two-sided CI, by ITT, descriptive analysis  Design

RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4 Naïve N = 35 Prior relapse N = 22 Prior partial Response N = 10 Prior null response N = 40 Median age, years Female26%14%028% HCV genotype 4a / 4d / other 35% / 24% / 41% 50% / 18% / 32% 30% / 30% / 40% 48% / 25% / 28% IL28B CC genotype21%5%00 Metavir F0-F1 / F2 / F3 / F4 57% / 17% / 20% / 6% 14% / 36% / 9% / 41% 20% / 30% / 0 / 50% 24% /22% / 16% / 38% HCV RNA log 10 IU/ml, median Discontinued treatment, N Lost to follow-up Withdrew RESTORE Baseline characteristics and patient disposition Moreno C. J Hepatol 2015;62:

( 70-95) % N ( ) Naïve 40 (25-55) (30-90) 10 Prior relapse Prior partial response Prior null response On-treatment failure, N32218 Virologic breakthrough, N41213 Relapse, N3126 Naïve Prior relapse Met RGT criteria 31/3520/22 W4 : HCV RNA undetectable 27/28 (96.4%) 17/18 (94.4%) W4 : HCV RNA detectable 2/31/1 SVR 12 in patients with HCV RNA < 25 IU/ml at W4 and undetectable at W12 (RGT) RESTORE RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4 SVR 12 (HCV RNA < 25 IU/ml), % (95% CI) Moreno C. J Hepatol 2015;62:

RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4  Resistance testing (NS3) in treatment failure –Available in 32/37 –28/32 with emergence of NS3 mutations at positions 80, 122, 155, 156 and/or 168 Most frequent profile : D168V alone or D168E ± mutations at position 80 RESTORE Moreno C. J Hepatol 2015;62:

RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4 N = 107 Serious adverse event Possibly related to SMV 5 (4.7%) 0 AE leading to discontinuation of SMV (valium overdose)1 (0.9%) Grade 3 adverse events6 (5.6%) Grade 4 adverse events1 (0.9%) Most common adverse events Influenza-like illness46% Asthenia42% Fatigue35% Adverse events of clinical interest Anemia10% Dyspnea11% Neutropenia5% Photosensitivity (all grade 1)2% Pruritus (no grade 3-4)21% Rash (no grade 3-4)14% RESTORE Adverse events during the SMV + PEG-IFN + RBV phase, N (%) Moreno C. J Hepatol 2015;62:

RESTORE Study: SMV + PEG-IFN  -2a + RBV for HCV genotype 4  Summary –In this open-label study of genotype 4 infection, 12 weeks of SMV weeks of PEG-IFN + RBV achieved an overall SVR 12 of 65% in treatment-naïve and prior relapsers SVR 12 was 83% and 86%, respectively, which is in line with SVR 12 rates observed in phase III studies of SMV + PEG-IFN + RBV in patients with genotype 1 Most of naïve and prior relapsers could stop PEG-IFN + RBV at W24 SVR 12 rates were similar across the different HCV genotype 4 subtypes, with slightly lower rates observed among patients with genotype 4d –Adverse events were mainly grade 1 or 2, with few serious adverse events and no deaths –Limitations No control arm RESTORE Moreno C. J Hepatol 2015;62: