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BROWSE SLIDES

Design

* Randomisation was stratified on genotype (1 or 4 or 6) and cirrhosis ( yes or no)
** Metavir F4 or fibroscan > 12.5 kPa or FibroTest > 0.75 + APRI > 2

Objective

• SVR₁₂ (HCV RNA < 15 IU /ml) by intention to treat analysis : superiority to historical SVR₁₂ of simeprevir + PEG-IFN + RBV (73%), at an overall 1-sided alpha value of 0.025, 99% power

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 15 IU/ml) , % (95% CI)

SVR₁₂ (HCV RNA < 15 IU/ml) by subgroup , % (95% CI)

SVR₁₂ in genotype 1 according to baseline NS3 and NS5A RAVs

All 11 patients with virologic failure had baseline HCV RNA > 800,000 IU/ml (selection of NS5A RAV in 10/11)

Baseline and emergent resistance variants in virologic failure cases

Adverse events, N (%)

Laboratory abnormalities, n (%)

Summary

• A 12-week regimen of the oral fixed dose combination of once-daily, single-tablet of grazoprevir/elbasvir, achieved an overall SVR₁₂ of 95%
  • High efficacy in genotypes 1 and 4
  • SVR₁₂ lower in genotype 6
  • High efficacy in cirrhotics (SVR₁₂ = 97.1%)
  • Lower efficacy observed among patients with high viral load (HCV RNA > 800,000 IU/ml)
• Overall virologic failure rate was 4%
  • Baseline NS3 RAVS did not affect efficacy
  • Association between virologic failure and the presence of baseline NS5A RAVs, which was most apparent in genotype 1a with baseline RAVs demonstrating > 5-fold potency reduction to elbasvir
  • Emergence of (additional) NS3 and/or NS5A RAVs at failure was common
• Grazoprevir/elbasvir was generally well-tolerated, with a similar safety profile in cirrhotic and non-cirrhotic patients
• Limitations
  • No active-control group