Although direct-acting antivirals (DAAs) are an effective therapy for patients with HCV, those who experience virologic failure with prior treatment remain a difficult-to-cure population.
 
Glecaprevir/pibrentasvir (G/P) has demonstrated efficacy and safety as a treatment for hepatitis C virus (HCV); however, data on the retreatment of patients who failed G/P are limited. In the ongoing MAGELLAN-3 phase 3b clinical trial, researchers are evaluating G/P plus sofosbuvir (SOF) plus ribavirin (RBV) as a treatment regimen in this patient population. According to the researchers, this is the first study of patients on a retreatment regimen indicated specifically for those who have had virologic failure following G/P treatment.
 
The retreatment regimen included once-daily G/P (300/120 mg) plus SOF (400 mg) and twice-daily, weight-based RBV.
 
In the study:
  • Patients with HCV genotype 1, 2, 4, 5, or 6 infection, without cirrhosis, who were naïve to NS3/4A protease and NS5A inhibitor 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 inhibitor prior to virologic failure with G/P received 16 weeks of treatment. 
Overall, sustained virologic response at post-treatment week 12 (SVR12) with the retreatment regimen was 96%, with no on-treatment virologic failures. All patients with HCV GT3 infection achieved SVR12 and 50% had multiple NS5A resistance-associated substitutions (RASs) at baseline, according to the study.
 
Both patients with HCV GT2 infection achieved SVR12 and neither had RASs at baseline other than the common NS5A M31 polymorphism. One patient with GT1a infection treated with the 16-week regimen relapsed at post-treatment week 4. The study demonstrated that the retreatment regimen of G/P plus SOF plus RBV was well tolerated with no treatment discontinuations.
 
According to the study, the results demonstrated that patients who previously failed G/P treatment can be successfully retreated.
 
“These results are an encouraging step on the path to HCV elimination, providing a treatment option for the increasingly small but important subpopulation of patients who fail highly effective DAA therapies such as G/P, and whose retreatment options are limited,” the researchers concluded in the study.
 
Reference
 
Wyles D, Weiland O, Weilert F, et al. Retreatment of patients who failed glecaprevir/pibrentasvir treatment for hepatitis C virus infection. Journal of Hepatology. 2019. Doi: https://doi.org/10.1016/j.jhep.2019.01.031