The FDA has granted breakthrough therapy status to the investigational, pan-genotypic regimen of glecaprevir/pibrentasvir (AbbVie) for the treatment of patients with chronic hepatitis C virus (HCV) infection who failed previous therapy with direct-acting antivirals (DAAs) in genotype 1 (GT1), including therapy with a nonstructural protein 5A (NS5A) inhibitor and/or a protease inhibitor.
According to the FDA, breakthrough therapy status is intended to expedite the development and review of therapies for serious or life-threatening conditions.
The breakthrough therapy designation for glecaprevir/pibrentasvir was supported by positive results from the MAGELLAN-1 trial. This ongoing phase 2, randomized, open-label, multicenter study was designed to evaluate the efficacy, safety, and pharmacokinetics of glecaprevir and pibrentasvir, with and without ribavirin (RBV), in adults with GT1 and GT4–6 chronic HCV infection who failed a prior DAA-containing therapy.
In part 1 of the study, 50 GT1 patients without cirrhosis who had failed therapy containing a protease inhibitor and/or an NS5A inhibitor, with or without an NS5B polymerase inhibitor, were randomly assigned to receive once-daily glecaprevir/pibrentasvir at doses of 200 mg/80 mg (arm A), 300 mg/120 mg with 800 mg RBV (arm B), or 300 mg/120 mg without RBV (arm C) for 12 weeks. The study’s primary efficacy endpoint was the sustained viral response at 12 weeks (SVR12). Patients who failed previous treatment for reasons other than breakthrough or relapse were excluded.
Ninety-one percent (20/22) of GT1 chronic HCV-infected patients who failed previous therapy with DAAs achieved SVR12 with glecaprevir/pibrentasvir with RBV in the primary intent-to-treat analysis. In addition, 86% (19/22) of GT1 patients who received glecaprevir/pibrentasvir without RBV achieved SVR12. This endpoint was also achieved by 95% of patients with and without RBV (20/21 and 19/20; respectively) in a modified intent-to-treat analysis, which excluded patients who did not achieve SVR12 for reasons other than virological failure.
Part 2 of the study is under way to examine once-daily glecaprevir (300 mg) and pibrentasvir (120 mg) without RBV in a larger group of DAA treatment-experienced patients, including those with compensated cirrhosis and with genotypes 4–6.