The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study
Liver Int. 2022 Feb 26. doi: 10.1111/liv.15211. Online ahead of print.
Fred Poordad1, Franco Felizarta2, Betty B Yao3, J Scott Overcash4, Tarek Hassanein5, Kosh Agarwal6, Edward Gane7, David Shaw8, Michael Waters4, Preethi Krishnan3, Andrew Topp3, Margaret Burroughs3, Frederik Nevens9
Author information
The Texas Liver Institute, University of Texas Health, San Antonio, Texas, USA.
Private Practice, Bakersfield, California, USA.
AbbVie Inc, North Chicago, Illinois, USA.
eStudySite, San Diego, California, USA.
Southern California GI and Liver Centers and Southern California Research Center, Coronado, California, USA.
Institute of Liver Studies, Kings College Hospital NHS Foundation Trust, London, UK.
New Zealand Liver Transplant Unit, University of Auckland, Auckland, New Zealand.
Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Department of Gastroenterology and Hepatology, University Hospital KULeuven, Leuven, Belgium.
Abstract
Background and aims: This study aimed to determine durability of sustained virologic response (SVR) in hepatitis C virus-infected participants treated with glecaprevir- and/or pibrentasvir-containing regimens.
Methods: M13-576, a rollover study, evaluated the durability of SVR in a follow-up period of approximately 3 years after hepatitis C virus genotype 1-6-infected participants received a glecaprevir- and/or pibrentasvir-containing regimen in previous phase 2/3 clinical trials. The primary efficacy endpoint was the percentage of participants maintaining SVR and the percentage of participants experiencing relapse or reinfections. Resistance-associated substitutions and safety outcomes related to liver progression were also assessed.
Results: Of 384 participants enroled, 377 participants were included in the as-observed population and 287 participants completed the study. In prior studies, 99.7% (376/377) of participants achieved SVR12; of those, an observed 99.5% (374/376) and 100% (286/286) completing the study, maintained SVR. After non-responder imputation of missing data, 286/376 participants (76%) maintained SVR. The participant previously not achieving SVR was a treatment-experienced male with compensated cirrhosis who had NS3 and NS5A substitutions at enrolment, which remained detectable for 12 months. Of the two participants not maintaining SVR, one was re-infected and one experienced late relapse at post-treatment week 60. Five participants (all with a fibrosis stage ≥F3) had hepatocellular carcinoma. No events were deemed related to glecaprevir/pibrentasvir.
Conclusions: Glecaprevir/pibrentasvir demonstrated long-term durability of efficacy after SVR12 was achieved. Hepatic-related decompensation events were not seen. Owing to low incidence of virologic failure, conclusions were not drawn on persistence of resistance-associated substitutions.