SURVEYOR-I Part 2

SURVEYOR-I Study - Part 2: ABT-493 + ABT-530 in genotype 1, 4, 5, 6 – Phase II

Poordad F. EASL 2016, Abs. SAT-157, J Hepatol 2016;64:S768 ; Gane E. EASL 2016, Abs SAT-135, J Hepatol 2016;64:S757, EASL 2016, Abs SAT-137, J Hepatol 2016;64:S758

Anti-HCV
Glecaprevir (ABT-493)
Pibrentasvir (ABT-530)
Genotype
2
3
Treatment history
Naive
IFN-Experienced
Cirrhosis
Yes
No

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Design


* Metavir F4 or Fibroscan > 14.6 kPa or FibroTest = 0.75 + APRI > 2, and Child-Pugh = 6

Objective

  • SVR12 (HCV RNA < 25 IU /ml), by ITT

Baseline characteristics

SRV12, ITT


* SVR12, ITTm = 100%: 1 patient discontinued study drug at W4 due to advanced carcinoma. HCV RNA was undetectable at the time of discontinuation ; achieved SVR4 but died prior to W12 post treatment
** 1 relapse at post-treatment W4: 60-year-old, white, female, genotype 1a, Fibroscan 20.9 kPa , baseline HCV RNA 6.25 log10 IU /ml, history of iv drug abuse and depression, HCV RNA undetectable by W2

Resistance analysis (population sequencing with 15% threshold)

  • Genotype 1, no cirrhosis: baseline RAVs in 76%: NS3 only in 48%,NS5A only in 15%, NS3 + NS5A in 12%
  • Genotype 1, cirrhosis:
    • Baseline RAVs in 41%: NS3 only in 30%,NS5A only in 7%, NS3 + NS5A in 11%
    • In patient with relapse
      • At baseline: I170V in NS3 and L31M in NS5A
      • At relapse: emergence of Y93N in NS5A (195-fold increase in EC50 to ABT-530)
  • Genotype 4, 5, 6: 5/22 genotype 4 had baseline NS5A RAVs, and 7/11 genotype 6 patients had baseline RAVs (NS3 only in 2,NS5A only in 4, NS3 + NS5A in 1)

Adverse events and laboratory abnormalities, %

Summary

  • High SVR rates were achieved in HCV genotype 1-infected patients with once daily combination of ABT-493 + ABT-530
    • By ITTm, all patients without cirrhosis achieved SVR12 after 8 weeks of treatment (97% by ITT)
    • In patients with compensated cirrhosis, SVR12 was 96% after 12 weeks of treatment
    • No impact on efficacy of baseline NS3 and/or NS5A RAVs
    • Only 1 of 11 patients with cirrhosis and baseline NS3 and NS5A RAVs experienced relapse
  • 100% SVR 12 was achieved in patients with HCV genotype 4, 5 or 6 following 12 weeks of ABT-493 + ABT-530
  • Adverse events were mostly mild in severity No discontinuation for adverse event related to study drug