Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis

Paul Y. Kwo, Fred Poordad, Armen Asatryan, Stanley Wang, David L. Wyles, Tarek Hassanein, Franco Felizarta, Mark S. Sulkowski, Edward Gane, Benedict Maliakkal, J. Scott Overcash, Stuart C. Gordon, Andrew J. Muir, Humberto Aguilar, Kosh Agarwal, Gregory J. Dore, Chih Wei Lin, Ran Liu, Sandra S. Lovell, Teresa I. NgJens Kort, Federico J. Mensa

Research output: Contribution to journalArticle

163 Scopus citations

Abstract

Background & Aims Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4 A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1–6 infection. Methods SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1–6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12 weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12). Results Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4–6 infection, respectively. Twelve-week treatment achieved SVR12 in 97–100%, 96–100%, 83–94%, and 100% in genotypes 1, 2, 3, and 4–6, respectively. Eight-week treatment with 300 mg glecaprevir plus 120 mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97–98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed. Conclusions Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1–6-infected patients without cirrhosis following 8- or 12-week treatment durations. Lay summary The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1–6 infection. This article describes results from two phase II trials investigating a range of doses at treatment durations of 8 or 12 weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well tolerated and significant laboratory abnormalities were rare. Clinical trial registration: clinicaltrials.gov Identifiers: NCT02243280 and NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280, http://www.clinicaltrials.gov/show/NCT01939197.

Original languageEnglish (US)
Pages (from-to)263-271
Number of pages9
JournalJournal of Hepatology
Volume67
Issue number2
DOIs
StatePublished - Aug 2017

Keywords

  • ABT-493
  • ABT-530
  • D-alanine transaminase
  • Direct-acting antiviral
  • Genotype
  • Hepatitis C, chronic
  • Interferons
  • Liver cirrhosis
  • Pangenotypic
  • SURVEYOR
  • Sustained virologic response

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis'. Together they form a unique fingerprint.

  • Cite this

    Kwo, P. Y., Poordad, F., Asatryan, A., Wang, S., Wyles, D. L., Hassanein, T., Felizarta, F., Sulkowski, M. S., Gane, E., Maliakkal, B., Overcash, J. S., Gordon, S. C., Muir, A. J., Aguilar, H., Agarwal, K., Dore, G. J., Lin, C. W., Liu, R., Lovell, S. S., ... Mensa, F. J. (2017). Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1–6 without cirrhosis. Journal of Hepatology, 67(2), 263-271. https://doi.org/10.1016/j.jhep.2017.03.039