Table of Contents
Drug Summary
Glecaprevir-pibrentasvir (Figure 1) and (Figure 2) is the first pangenotypic NS3/4A protease inhibitor-NS5A inhibitor combination to be approved that offers a potent treatment option for the vast majority of persons with chronic hepatitis C, including an 8-week option for treatment-naïve individuals. This drug is not an option for persons with decompensated cirrhosis (Child B/C) given the presence of the protease inhibitor. In the main registration trials, sustained virologic response rates for 8 or 12 weeks of glecaprevir-pibrentasvir for genotypes 1, 2, 5 or 6 were in the range of 98-100% with very few if any on-treatment virologic breakthroughs or post-treatment relapses.
Adverse Effects
The most common adverse effects, observed in at least 10% of phase 3 trial participants, were headache and fatigue.
Class and Mechanism
Glecaprevir (GLE, formerly ABT-493) is an NS3/4A protease inhibitor that prevents the cleavage of the HCV polyprotein. It has potent in vitro activity (on the order of less than or equal to 5 nanomolar), across the HCV genotypes including common HCV genotype 1 variants that have substitutions (at Q80, R155 and D168) conferring resistance to older-generation HCV protease inhibitors. Pibrentasvir (PIB, formerly ABT-530) is a next-generation NS5A inhibitor with pangenotypic activity in vitro; it maintains potent antiviral activity against common HCV NS5A single-position variants that confer resistance to first-generation NS5A inhibitors, including daclatasvir, ledipasvir, and ombitasvir.
Indications
The 8-week course of glecaprevir-pibrentasvir is indicated for treatment-naïve persons with genotypes 1-6 HCV, including individuals without cirrhosis and those with compensated cirrhosis (Child-Pugh A). For treatment-experienced persons, the treatment course varies from 8 to 16 weeks, based on HCV genotype, the prior treatment regimen, and cirrhosis status. For complete information on glecaprevir-pibrentasvir-related indications, see the Indications and Usage section in the Glecaprevir-Pibrentasvir (Mavyret) Prescribing Information.
Dosing
Each fixed-dose tablet contains 100 mg of glecaprevir and 40 mg of pibrentasvir. The recommended oral dosage of glecaprevir-pibrentasvir in adults is 3 tablets taken at the same time once daily with food (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg).
Cost and Medication Access
AbbVie has an active glecaprevir-pibrentasvir patient assistance program for eligible persons with hepatitis C who do not have insurance or do not have coverage through Medicaid or Medicare. Information regarding the AbbVie glecaprevir-pibrentasvir patient assistance program can be obtained at the myAbbVie Assist website or by phone at 1-800-222-6885.
Key Drug Interactions
For complete information on glecaprevir-pibrentasvir-related drug interactions, see the Drug Interactions section in the Glecaprevir-Pibrentasvir (Mavyret) Prescribing Information.
Figures
Figure 1. Fixed-Dose Tablet of Glecaprevir-Pibrentasvir (Mavyret)
Photo: Andrew Karpenko, University of Washington
Figure 2. Glecaprevir-Pibrentasvir (Mavyret) Packaging
This photograph is courtesy of AbbVie