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BROWSE SLIDES

Design

** Liver biopsy with Metavir = F3 or Ishak = 4, or Fibrotest ® = 0.48 + APRI = 1

• 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

• Primary endpoint : SVR₁₂ > 30% than historical control (adjusted rate of 60%), with a 2-sided significance level of 0.025, 90% power
• Secondary end-point : non inferiority of LDV/SOF 8W : SVR₁₂ by intention to treat analysis (significance level of 2.5%, lower margin of the 95% CI for the difference = 12%)

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)
• LDV/SOF 8W non inferior to LDV/SOF + RBV 8W (difference 0.9% (95% CI : - 3.9 to 5.7 ))
• LDV/SOF 8W non inferior to LDV/SOF 12W (difference - 1.4% (95% CI : - 6.4 to 3.6 ))

Virologic failure

• Virologic breaktrough : None
• Post-treatment relapse
  • 11 (5%) in the LDV/SOF 8W group
  • 9 (4%) in the LDF-SOV + RBV 8W group
  • 3 (1%) in the LDV/SOF 12W group
• NS5A resistant variants (deep sequencing)
  • Baseline resistance in 116 (18%) of 647 patients tested
  • SVR₁₂ in 104 (90%) of the 116 patients with NS5A resistance
  • 15 of the 23 patients (65%) with relapse had NS5A resistance at relapse
    • 9/15 had variants present at baseline
• No S282T NS5B-resistant variants detected at baseline or after treatment

Adverse events

Summary

• In this phase III trial, all 3 groups of previously untreated patients, with HCV genotype 1 infection without cirrhosis, who received treatment with LDV/SOF, had rates of SVR₁₂ that were higher than 90%
• LDV/SOF 8 weeks was non inferior to LDV/SOF 12 weeks or to LDV/SOF + RBV 8 weeks, suggesting that adding RBV did not improve SVR while worsening treatment burden and increasing toxicity
• SVR₁₂ was not different in genotype 1a and 1b
• Relapse occurred in few patients, more commonly in 8-week groups
  • None had evidence of mutations conferring resistance to SOF
  • Mutations associated with resistance to NS5A inhibitors were present in most patients at baseline and at the time of relapse
• In conclusion, 8 weeks of treatment with a single-tablet regimen of LDV/SOF resulted in a high rate of SVR₁₂ among previously untreated patients with HCV genotype 1 infection without cirrhosis