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LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Design Open-label W24 Chronic HCV infection Genotype 1 Failure to achieve SVR on LDV/SOF-containing regimen Compensated cirrhosis (liver biopsy or Fibrotest > 0.75 + APRI > 2) allowed No HBV or HIV co-infection N = 41 LDV/SOF 90/400 x 1 qd SVR12 Objective – Primary endpoint : SVR12 (HCV RNA < 15 IU/ml) by intention to treat, with 2-sided 95% CI, no statistical hypothesis LDV/SOF Failure Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Baseline characteristics N = 41 Mean age, years 58 Female 17% IL28B CC genotype 7% HCV RNA log10 IU/ml, mean 6.2 Cirrhosis 46% Genotype 1a 83% Prior HCV treatment LDV/SOF + RBV LDV/SOF + GS-9669 80% 20% Prior HCV treatment duration 8 weeks Presence of NS5A RAVs 30 (73%) 19/30 (63%) Prior HCV treatment duration 12 weeks Presence of NS5A RAVs 11 (27%) 11/11 (100%) LDV/SOF Failure Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF SVR12 (HCV RNA < 15 IU/ml) 100 % 100 71 75 68 74 100 80 100 80 69 60 50 46 50 33 25 0 N 41 22 19 30 11 11 30 11 16 14 All No Yes 8W 12W No Yes None 1 ≥2 Cirrhosis Prior treatment duration Baseline NS5A RAVs Number of NS5A RAVs 5 5 6 Q30R L31M Y93H/N or M28T Type of single NS5A RAVs LDV/SOF Failure Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF NS5B Resistance analysis – Baseline : No NS5B resistance associated (S282T) or treatmentemergent (L159F, V321A) variants were detected – At virologic failure : NS5B variants detected in 4 of 12 (33%) patients • S282T (N = 2) • L159F (N = 1) • Double-mutant S282T + L159F (N = 1) Adverse events – – – – – Serious adverse events : 3 Discontinuation due to adverse event : 0 Grade 3 adverse events : 3 (none related to study drug) Adverse events in ≥ 10% of patients : headache, fatigue Grade 3 laboratory abnormality : 2 LDV/SOF Failure Lawitz E. EASL 2015, Abs. O005 LDV/SOF Failure Study: LDV/SOF for retreatment of genotype 1 with prior failure to LDV/SOF Summary – 71% of patients who failed prior LDV/SOF-containing regimens achieved SVR12 when retreated with LDV/SOF for 24 weeks – The presence of baseline NS5A RAV(s), which was more likely to develop with longer prior LDV/SOF treatment, was associated with virologic failure – Emergence of S282T was observed in 3 of 12 virologic failures LDV/SOF Failure Lawitz E. EASL 2015, Abs. O005