ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.

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Presentation transcript:

ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection Genotype 1 HCV RNA ≥ 10,000 IU/ml Treatment-naïve Cirrhosis** allowed No HBV or HIV co-infection LDV/SOF LDV/SOF + RBV * Randomisation stratified on genotype (1a or 1b) and cirrhosis N = 214 N = 217 SVR 12 ** Liver biopsy with Metavir F4 or Ishak > 5, or Fibrotest® > APRI > 2, or Fibroscan kPa > 12.5 –Co-formulated ledipasvir-sofosbuvir (LDV 90mg/SOF 400 mg) : 1 pill qd –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)  Objective –SVR 12 > 13% than historical control with telaprevir or boceprevir (adjusted rate of 60%), with a 2-sided significance level of , 91% power SVR 12 Afdhal N. NEJM 2014; 370:

LDV/SOF 12W N = 214 LDV/SOF + RBV 12W N = 217 LDV/SOF 24W N = 217 LDV/SOF + RBV 24W N = 217 Mean age, years52 53 Female41% 36%45% Race : white/black87% / 11%87% / 12%82% / 15%84% / 12% Body mass index, mean27 26 HCV genotype : 1a / 1b67% / 31%68% / 31%67% / 31%66% / 33% Cirrhosis16%15% 17% IL28B CC genotype26%35%24%34% HCV RNA log 10 IU/ml, mean Completed treatment Baseline characteristics and patient disposition ION-1 ION-1 Study: LDV/SOF + RBV for genotype 1 Afdhal N. NEJM 2014; 370:

SVR 12 (HCV RNA < 25 IU/mL) % All groups had superior SVR 12 than the historical control of 60% (p < for all comparisons) LDV/SOF 12WLDV/SOF + RBV 12W LDV/SOF 24WLDV/SOF + RBV 24W SVR 12 : 99% to 100% in patients without cirrhosis ; 97% to 100% in patients with cirrhosis Virologic failure  Virologic breaktrough: 1 in LDV/SOF 24W  Post-treatment relapse –1 in LDV/SOF 12W –1 in LDV/SOF 24W  NS5A resistant variants –Baseline resistance in 140 (16%) of 861 patients tested –SVR 12 in 135 (96%) of 140 patients with NS5A resistance –2 of the 3 patients with virologic failure had baseline NS5A resistance ION-1 ION-1 Study: LDV/SOF + RBV for genotype 1 Afdhal N. NEJM 2014;370:

LDV/SOF 12W N = 214 LDV/SOF + RBV 12W N = 217 LDV/SOF 24W N = 217 LDV/SOF + RBV 24W N = 217 Discontinuation for adverse event004 (2%)6 (3%) Serious adverse event17187 Adverse event in ≥ 10% in either group Fatigue Headache Insomnia Nausea Asthenia Diarrhea Rash Irritability Cough Pruritus Anemia 21% 25% 8% 11% 7% 11% 7% 5% 3% 5% 0 36% 23% 21% 17% 11% 8% 10% 8% 10% 12% 24% 25% 12% 13% 9% 11% 7% 8% 7% 4% 0 38% 30% 22% 15% 12% 6% 12% 11% 12% 9% 10% Adverse events ION-1 ION-1 Study: LDV/SOF + RBV for genotype 1 Afdhal N. NEJM 2014;370:

 Summary –12 weeks of the single-tablet regimen of LDV/SOF was a highly effective treatment for a broad range of patients with HCV genotype 1 infection who had not been treated previously –No additional benefit appeared to be associated with the addition of RBV or with extension of the duration of treatment to 24 weeks addition of RBV increased toxicity without providing additional efficacy –Safety of LDV/SOF was similar to the one previously reported with SOF alone –Virologic failure was extremely rare in this study population, occurring in only 0.3% of patients (3 of 865). The 2 patients with relapse had no evidence of mutations conferring resistance to SOF Both patients had mutations associated with resistance to NS5A inhibitors both at baseline and at the time of relapse. ION-1 ION-1 Study: LDV/SOF + RBV for genotype 1 Afdhal N. NEJM 2014;370: