By Reuters Staff
August 22, 2019
NEW YORK (Reuters Health) – The direct-acting antiviral (DAA) combination of glecaprevir and pibrentasvir is effective in patients with genotype 1 hepatitis C virus (HCV) infection after failure of treatment with sofosbuvir plus an NS5A inhibitor, according to results from a new open-label trial.
The combination of glecaprevir (a protease inhibitor) and pibrentasvir (an NS5A inhibitor) is approved in the U.S. for genotype-1-HCV-infected patients who don’t respond to treatment including an NS5A inhibitor but have not been treated with protease inhibitors.
Dr. Anna S. Lok of the University of Michigan, in Ann Arbor, and colleagues from 30 centers in the U.S. investigated the safety and efficacy of 12 and 16 weeks of glecaprevir/pibrentasvir (G/P), with or without ribavirin, in their phase 3b randomized study of 177 patients with chronic HCV-genotype-1 infection who received previous treatment with sofosbuvir (a nucleoside polymerase inhibitor) plus an NS5A inhibitor.
Sustained virologic response 12 weeks after completion of treatment (SVR12), the primary endpoint, was achieved by 91.5% (162/177) of patients, including 90% of those without cirrhosis treated for 12 weeks (group A); 94% of those without cirrhosis treated for 16 weeks (group B); 86% of those with compensated cirrhosis treated with G/P and ribavirin for 12 weeks (group C); and 97% of those with compensated cirrhosis treated for 16 weeks (group D).
Baseline NS5A-resistance-associated substitutions (RASs) were present in 76% of patients at baseline, but only 7% of these experienced treatment failure. There was no association between individual NS5A RAS and reduced SVR12 or between patients with and without baseline NS5A RASs, suggesting that testing for RAS prior to retreatment is not beneficial, the researchers report in Gastroenterology, online August 8.
Overall, G/P was well tolerated, and no patient discontinued G/P because of adverse events or lab abnormalities, although about two-thirds experienced at least one adverse event (most commonly, fatigue, nausea, and headache).
“These results are consistent with the relatively small MAGELLAN 1 Part 2 dataset and support (Food and Drug Administration) approval of 16-week G/P as a retreatment option for genotype 1 sofosbuvir plus NS5A inhibitor treatment failures,” the authors conclude.
“Our results do not apply to patients with decompensated cirrhosis in whom G/P is contraindicated,” they add.
AbbVie provided funding and study drug, employed three of the authors and had various relationships with several others.
Dr. Lok was unable to respond to a request for comment.