Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study

Liver Int. 2022 Jun;42(6):1278-1286. doi: 10.1111/liv.15211. Epub 2022 Mar 14.

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.

Trial registration: ClinicalTrials.gov NCT02441283.

Keywords: glecaprevir; hepatitis C; pibrentasvir; sustained virologic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoisobutyric Acids
  • Antiviral Agents / therapeutic use
  • Benzimidazoles
  • Cyclopropanes
  • Follow-Up Studies
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic* / complications
  • Humans
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Male
  • Neoplasm Recurrence, Local
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Pyrrolidines
  • Quinoxalines / therapeutic use
  • Sulfonamides
  • Sustained Virologic Response

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • Proline
  • Leucine
  • glecaprevir

Associated data

  • ClinicalTrials.gov/NCT02441283