Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection

Curative treatment of patients who previously failed hepatitis C virus (HCV) therapies is critical to achieving HCV elimination. Glecaprevir/pibrentasvir (G/P) demonstrated high rates of sustained virologic response at post-treatment week 12 (SVR12) in patients with HCV infection; however, retreatment of patients who failed G/P has yet to be evaluated. MAGELLAN-3 is an ongoing, open-label, phase IIIb trial evaluating the efficacy and safety of G/P plus sofosbuvir (SOF) plus ribavirin (RBV) as a retreatment regimen for patients who had virologic failure with G/P in an AbbVie study. Patients with HCV genotype (GT) 1, 2, 4, 5 or 6 infection, without cirrhosis, and naive to NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 12 weeks of treatment; patients with GT3, and/or compensated cirrhosis, and/or experience with NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 16 weeks of treatment. The primary efficacy endpoint was the SVR12 rate. Safety, tolerability, and presence of resistance-associated substitutions (RASs) were assessed. To date, 23 patients enrolled: 30% (7/23), 9% (2/23), and 61% (14/23) of patients had GT1, 2, and 3 infections, respectively; 30% (7/23) of patients had compensated cirrhosis, and 91% (21/23) had baseline RASs in NS5A. The SVR12 rate was 96% (22/23); 1 patient with GT1a infection and compensated cirrhosis had virologic failure. One unrelated serious adverse event (AE) of symptomatic cholelithiasis occurred. There were no treatment discontinuations. Retreatment of G/P virologic failures with G/P plus SOF plus RBV for 12 or 16 weeks was well-tolerated and highly efficacious, regardless of HCV genotype or baseline RASs.