Although direct-acting antiviral (DAA) therapies for chronic hepatitis C virus 
(HCV) infection have demonstrated high rates of sustained virologic response, 
virologic failure may still occur, potentially leading to the emergence of viral 
resistance, which can decrease the effectiveness of subsequent treatment. 
Treatment options for patients who failed previous DAA-containing regimens, 
particularly those with nonstructural protein 5A inhibitors, are limited and 
remain an area of unmet medical need. This phase 2, open-label study 
(MAGELLAN-1) evaluated the efficacy and safety of glecaprevir (GLE) + 
pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1-infected patients with 
prior virologic failure to HCV DAA-containing therapy. A total of 50 patients 
without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 
300 mg GLE + 120 mg PIB with 800 mg once-daily RBV (arm B), or 300 mg GLE + 120 
mg PIB without RBV (arm C). By intent-to-treat analysis, sustained virologic 
response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence 
interval 61-100), 95% (21/22, 95% confidence interval 78-99), and 86% (19/22, 
95% confidence interval 67-95) of patients in arms A, B, and C, respectively. 
Virologic failure occurred in no patients in arm A and in 1 patient each in arms 
B and C (two patients were lost to follow-up in arm C). The majority of adverse 
events were mild in severity; no serious adverse events related to study drug 
and no relevant laboratory abnormalities in alanine aminotransferase, total 
bilirubin, or hemoglobin were observed.
CONCLUSION: The combination of GLE and PIB was highly efficacious and well 
tolerated in patients with HCV genotype 1 infection and prior failure of 
DAA-containing therapy; RBV coadministration did not improve efficacy. 
(Hepatology 2017;66:389-397).