ENDURANCE-1

ENDURANCE-1 Study: glecaprevir/pibrentasvir in genotype 1 without cirrhosis

Zeuzem S. AASLD 2016, Abs. 253

Anti-HCV
Glecaprevir (ABT-493)
Pibrentasvir (ABT-530)
Genotype
1
Treatment history
Naive
IFN-Experienced
Cirrhosis
No
Special population
HIV co-infection

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Design


* Fibroscan® < 12.5 kPa or FibroTest® = 0.48 + APRI < 1

  • GLE/PIB: 100/40 mg 3 tablets QD

Objectives (SVR12)

  • Non-inferiority of the 12-week regimen, by ITT-PS (exclusion of HIV and prior SOF), with lower margin of the 2-sided CI > 91% (historical rate)
  • Non-inferiority of the 12-week regimen, by ITT-PS-PP (ITT-PS + exclusion of premature discontinuation or virologic failure prior to W8 and missing data in the SVR12 window), with lower margin of the 95% CI for the difference = 5%
  • Non-inferiority of the 8-week regimen, by ITT-PS, with a lower margin of the 95% CI for the difference = 5%
  • Secondary endpoints
  • Efficacy in HIV-co-infection and in patients with prior SOF treatment, by ITT
  • Virologic failure and relapse
  • Resistance analysis (15% detection threshold)
  • Safety

Baseline characteristics

Primary Endpoints (SVR12)


ITT-PS: ITT population, excluding HIV co-infected and SOF-experienced patients
ITT-PS-PP: ITT-PS population excluding patients with premature discontinuation or virologic failure prior to W8, and missing data in the SVR12 window

* 1 patient with genotype 1a in the 8W treatment arm experienced on-treatment virologic failure at D29

Secondary efficacy endpoints (SVR12): ITT population

ITT population: all patients receiving study drug ; none excluded
* 1 patient experienced on-treatment virologic failure, 1 patient discontinued on D2 due to non-compliance, 1 patient missing SVR12 data
** 1 patient missing SVR12 data

Adverse events and laboratory abnormalities, N (%)


* On treatment: pneumonia aspiration, atrial fibrillation, angina unstable, radius fracture, transient ischemic attack, irritable bowel syndrome. Post-treatment: bronchitis, uterine myoma, suicide attempt.
** dandruff, anxiety and amnesia, all deemed not related to therapy.
1 death occurred during post-treatment period due to an unknown cause considered unrelated to study drug

Summary

  • 99-100% of genotype 1-infected patients without cirrhosis achieved SVR12 with 8 or 12 weeks of glecaprevir / pibrentasvir (GLE/PIB)
  • 8-week treatment was non-inferior to 12-week treatment (all 3 primary endpoints were met)
  • SVR12 rates were high regardless of
    • HIV-1 co-infection (limitation: 5% of the study population)
    • prior treatment experience
    • baseline HCV RNA
    • presence of baseline polymorphisms
    • or other factors
  • GLE/PIB was well tolerated
    • Only 1 patient (0.1%) discontinued study drugs for adverse event
    • No significant laboratory abnormalities