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Study 337-1119 : LDV/SOF in genotype 5

Study evaluating the efficacy and safety of LDV/SOF in patients with genotype 5 chronic HCV infection. Results showed high SVR12 rates and low incidence of adverse events. NS5A and NS5B resistance-associated variants had no impact on treatment response.

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Study 337-1119 : LDV/SOF in genotype 5

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  1. Study 337-1119: LDV/SOF in genotype 5 • Design W12 Open-label ≥ 18 years Chronic HCV infection Genotype 5 HCV RNA ≥ 10,000 IU/ml Treatment-naïve or experienced Compensated cirrhosis allowed Creatinine clearance ≥ 60 ml/min No HBV or HIV co-infection N = 41 SVR12 • Co-formulated ledipasvir-sofosbuvir (LDV 90 mg/SOF 400 mg): 1 pill QD • Objective • Primary endpoint: SVR12 (HCV RNA < 15 IU/ml), with 2-sided 95% CI Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

  2. Study 337-1119: LDV/SOF in genotype 5 Baseline characteristics, patient disposition and outcome Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

  3. Study 337-1119: LDV/SOF in genotype 5 • Adverse events, N (%) Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

  4. Study 337-1119: LDV/SOF in genotype 5 Additional outcome • No grade 3 or 4 laboratory abnormalities • Emergent laboratory abnormalities: total bilirubin < 1.5 ULN: 10% ; hemoglobin 100-109 g/dl: 2% ; lipase > 1.5-3.0 ULN: 2% ; platelets 100 000 to 125 000/mm3: 2% • Successful deep sequencing in 39/41 patients • NS5A: 8/39 (21%) had RAVs at baseline(SVR12 in 7/8 patients) • Q30R/L (N = 2; 2.5% and 3.9% of viral population) • L31M/F (N = 4; 29.5% to > 99% of viral population) • P58S (N = 2; 9.9% and 94.6% of viral population) • NS5B: 9/39 (23%) had RAVs at baseline (SVR12 in 9/9 patients) • N142T (N = 7 ; 1.1% to 19.2% of viral population) • M289I (N = 2 ; 7.6% and 98.3% of viral population) Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

  5. Study 337-1119: LDV/SOF in genotype 5 Viral relapse (n = 2) • Man, 72-year old, treatment-experienced (partial response), IL28B TT genotype, cirrhosis, HCV RNA 170 000 IU/ml. At baseline: NS5A RAV L31M (> 99% of viral population). HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4 At relapse • NS5A: L31M, no additional RAV • NS5B: emergence of S282T (2% viral population) and M289I (16% viral population) • Woman, 56-year old, naïve, no cirrhosis, IL28B TT genotype, HCV RNA 180 000 UI/ml. HCV RNA < limit of quantification at W1 and undetectable from W2 to the end of treatment. Relapse at post-treatment W4. Failure to baseline and post-treatment NS5A and NS5B amplification Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

  6. Study 337-1119: LDV/SOF in genotype 5 • Summary • This prospective, open-label study is the first to assess a regimen consisting of only directly acting antivirals in patients with HCV genotype 5 infection • A fixed-dose combination regimen with ledipasvir-sofosbuvir once per day for 12 weeks resulted in SVR12 in 39 (95%) of 41 patients • The 2 relapses had the IL28B TT genotype, one was naïve with no cirrhosis, one was treatment-experienced with cirrhosis and NS5A RAV L31M at baseline • Overall, the presence of NS5A RAVs and NS5B N142T and M289I had no meaningful effect on the SVR12 for LDV/SOF in genotype 5 • No patients discontinued treatment because of an adverse event. Only one serious adverse event, worsening depression, was reported, and was deemed to be unrelated to study treatment Abergel A. Lancet Infect Dis. 2016;16:459-64 337-1119

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