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Design

* Randomisation only in genotype 1, 2, 3 and 4, stratified on genotype, cirrhosis (yes or no) and prior treatment-experience (naïve or IFN-experienced) ; No randomisation (open-label SOF/VEL/VOX) for other genotypes
** Metavir F4 or Ishak 5-6 or Fibroscan ® > 12.5 kPa or Fibrotest ® > 0.75 + APRI > 2

Objective

• SVR₁₂ (HCV RNA < 15 IU/mL), by ITT: non-inferiority of SOF/VEL/VOX (wo-sided significance level of 5%, lower margin of the 95% CI for the difference = - 5 %, 95% power)

Baseline characteristics and patient disposition

SVR₁₂ overall and in genotype 1, %

* Difference (2-sided 95% CI) : -3.4 % (-6.2% to -0.6%) » non inferiority not met

SVR₁₂ in genotype 2 to 6, %

SVR₁₂ by cirrhosis status, %

SVR₁₂ by baseline RASs, %

* RASs were analyzed using a 15% cut off

• All 64 patients with baseline NS5B nucleoside inhibitor RASs achieved SVR₁₂

Impact of baseline NS5A RAS

• For patients with genotype 1a, SVR₁₂ with SOF /VEL/ VOX 8 weeks
  • 89% if baseline RASs
  • 95% if no baseline RASs
  • 88% if baseline Q80K
  • 94% if absence of baseline 80K

Viral resistance testing at failure

• Of the 21 patients who relapsed in the SOF/VEL/VOX group, 1 had treatment-emergent NS5A resistance-associated substitutions Q30R and L31M
• Among patients receiving SOF/VEL, 1 of the 3 patients who relapsed had the Y93N variant, which is associated with resistance to NS5A inhibitors, at relapse

Adverse events

*1 upper respiratory tract infection and 1 Clostridium difficile infection, both not related to the study medication

Summary

• SOF/VEL/VOX for 8 weeks resulted in a 95% SVR₁₂ rate in DAA-naïve genotype 1-6 patients with and without cirrhosis
  • Did not meet non-inferiority as compared to the 98% SVR₁₂ rate with SOF/VEL for 12 weeks
  • The difference between the regimens was largely attributed to more relapses among patients with genotype 1a infection in the SOF/VEL/VOX group
• SOF/VEL/VOX and SOF/VEL were safe and well tolerated
  • Mild gastrointestinal adverse events (nausea and diarrhea) were associated with treatment regimens that included VOX
  • There was no evidence of VOX-related hepatotoxicity
• These findings in DAA-naïve patients with or without cirrhosis underscore the very high rates of SVR conferred by SOF/VEL across all HCV genotypes
  • SOF/VEL/VOX for 8 weeks provides a highly efficacious and well-tolerated short-duration regimen in patients for whom adherence to a longer duration regimen may be challenging