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BROWSE SLIDES

Design

* Randomisation was stratified on genotype (1a or 1b), IL28B (CC or non-CC), cirrhosis (yes or no)
** Liver biopsy or Fibroscan > 14.6 kPa

⁽¹⁾ : 24 weeks if undetectable HCV-RNA at W4 and W12 ( eRVR ) ; additional 24 weeks of PEG-IFN + RBV otherwise
⁽²⁾ : 12 weeks + 12 weeks (if eRVR ) or 36 weeks of PEG-IFN + RBV

• DCV: 60 mg qd ; TVR 750 mg tid ; PEG-IFNα-2a: 180 µg SC once weekly
• RBV: 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg)

Objective

• Primary endpoint: SVR₁₂ (HCV RNA < 25 IU /ml) , with 2-sided 95% CI, noninferiority of DCV vs TVR in genotype 1b, lower margin of -12%, 91% power

Baseline characteristics and patient disposition

SVR₁₂ (HCV RNA < 25 IU/ml), mITT

• Difference between treatment arms : 4.3% (95% CI: -3.3% to 11.9%) » noninferiority

SVR₁₂ in genotype 1b, by subgroups, mITT

Resistance analysis in genotype 1b

• NS5A population-based sequencing data
  • At baseline, N = 249/268
    • 43 (17.5%): = 1 of NS5A polymorphisms L28M/V, R30H/Q, L31M or Y93H
  • SVR12: 72.1% if NS5A polymorphisms vs 87% if no NS5A polymorphisms
  • At virologic failure, N = 32/40
    • Same NS5A RAVs at baseline and failure, N = 2
    • Treatment-emergent NS5A RAVS, N = 30
      • L31F/I/M/V, N = 22
      • Y93H, N = 21
      • L31 and Y93 together, N = 18

Adverse events, N or %

* 1 case of DRESS in each group, ** 5 cases of anemia

Grade 3 or 4 emergent laboratory abnormalities, N (%)

Safety secondary endpoints

• Hemoglobin < 10 g/dl in genotype 1b significantly lower in DCV vs TVR group (18.3% vs 47.4% ; 95% CI for difference: - 38.3% to – 19.4%)
• Grade 1-4 rash in genotype 1 not significantly different: 23.1% for DCV vs 34.5% for TVR (grade 3-4: 1.0% vs 3.5%)

Summary

• This head-to-head comparison of two classes of DAAs in treatment naive genotype 1b infected patients demonstrates that DCV + PEG-IFN + RBV is noninferior to TVR + PEG-IFN + RBV for SVR₁₂
• High SVR₁₂ was achieved in genotype 1b infected patients across all subgroups of baseline factors known to affect response rates to PEG-IFN + RBV (cirrhosis, IL28B genotype, age, sex, baseline viral load)
  • In difficult-to-cure patients with cirrhosis, SVR₁₂ was higher with DCV + PEG-IFN + RBV than with TVR+ PEG-IFN + RBV (76.9% vs 66.7%)
• Post treatment relapse was more frequent with TVR than with DCV (15% vs 5%), for genotype 1b
• SVR 12 with DCV + PEG-IFN + RBV was lower and virologic failure was more frequent in patients infected with genotype 1a
  • Lower resistance barrier of DCV in genotype 1a ?
• DCV + PEG-IFN + RBV was generally well tolerated, with a significantly lower rate of anemia, and an observed lower rate of rash-related events compared with TVR+ PEG-IFN + RBV