DOWNLOAD THIS SLIDE KIT

BROWSE SLIDES

Design

** Liver biopsy with Metavir F4 or Ishak > 5, or Fibrotest ® > 0.75 + 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

• Primary endpoint : SVR₁₂ > 45% than historical control (adjusted rate of 25%), with a 2-sided significance level of 0.0125, 99% power

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 25 IU/ mL)

• All groups had superior SVR₁₂ than the historical control of 25% (p < 0.001 for all comparisons)
• In patients with cirrhosis, SVR₁₂ was higher with 24 weeks vs 12 weeks of LDV/SOF (p = 0.007)
• Genotype 1a vs 1b : SVR₁₂ with 12 weeks : 95.4% vs 93.5% ; with 24 weeks : 99% vs 100 %

Virologic outcome - Mutivariate analysis of predictors of SVR₁₂

Virologic failure

• Virologic breaktrough : 1 in LDV/SOF + RBV 24W (non adherence)
• Post-treatment relapse
  • 0 in the 24-weeek groups
  • 7 (6%) in LDV/SOF 12W and 4 (4%) in LDV/SOF + RBV 12W
• NS5A resistant variants (deep sequencing)
  • Baseline resistance in 62 (14%) of 439 patients tested : SVR₁₂ in 55/62 (89%)
  • 6 of the 11 patients (55%) with relapse had baseline NS5A resistance
  • All 11 patients had NS5A resistant variants at relapse
  • Similar viral kinetics during early phase of treatment in patients with or without NS5A variants
• No S282T NS5B-resistant variants detected at baseline or after treatment

Adverse events

Summary

• 12 or 24 weeks of the single-tablet regimen of LDV/SOF was a highly effective treatment for patients with HCV genotype 1 infection who had not had a SVR after prior IFN-based treatment, including protease inhibitor
  • Rates of SVR₁₂ (94 to 99%) were similar with 12 or 24 weeks of treatment, with no additional benefit of RBV addition
  • Rates of SVR₁₂ were high (92 to 100%) in difficult-to-treat subgroups : IL28B non-CC, prior nonresponse to IFN-based regimen, including PI-based
  • In the 12-week groups, lower rate of SVR₁₂ in patients with cirrhosis
• LDV/SOF was not associated with any new or characteristic adverse events
  • Rate of AE was lower in 12-week LDV/SOF group vs the 3 other groups
• Relapse occurred in 11 patients (5%) in the 12-week groups
  • None had evidence of mutations conferring resistance to SOF
  • Mutations associated with resistance to NS5A inhibitors were present in 6/11 patients at baseline and in all at the time of relapse