Highlights
- •An all oral, once-daily, RBV-free, pangenotypic HCV treatment option is described.
- •8- or 12-week treatment with glecaprevir + pibrentasvir yielded high rates of SVR12.
- •Treatment was well-tolerated with a favorable safety profile.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: April 13, 2017
Accepted:
March 27,
2017
Received in revised form:
March 16,
2017
Received:
October 7,
2016
Identification
Copyright
© 2017 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
