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BROWSE SLIDES

Design

* Randomisation stratified on genotype (1a or 1b) and cirrhosis

• 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

• SVR₁₂ > 13% than historical control with telaprevir or boceprevir (adjusted rate of 60%), with a 2-sided significance level of 0.0125, 91% power

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 25 IU/ mL)

All groups had superior SVR₁₂ than the historical control of 60% (p < 0.001 for all comparisons)
SVR₁₂ : 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
  • SVR₁₂ in 135 (96%) of 140 patients with NS5A resistance
  • 2 of the 3 patients with virologic failure had baseline NS5A resistance

Adverse events

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