Glecaprevir/pibrentasvir was highly effective and well tolerated for the treatment of hepatitis C virus genotype 1 infection in patients who previously failed treatment with direct-acting antivirals, according to the results of the phase 2 open-label MAGELLAN-1 study.
Glecaprevir/pibrentasvir (AbbVie) is an investigational pan-genotypic regimen that combines two antiviral agents — 300 mg of glecaprevir, an NS3/4A protease inhibitor, and 120 mg of pibrentasvir, an NS5A inhibitor — that are administered once daily in three oral tablets. The FDA accepted the new drug application for the regimen and granted it priority review last week.
“The once-daily regimen of glecaprevir and pibrentasvir was well-tolerated with no serious adverse events related to study drug, no discontinuations due to adverse events, and no relevant laboratory abnormalities,” Fred Poordad, MD, of the Texas Liver Institute at University of Texas Health Science Center in San Antonio, and colleagues wrote. “It also resulted in high rates of [sustained virologic response (SVR)] with or without coadministration of [ribavirin] in patients with HCV [genotype 1] infection and prior DAA therapy experience.”
Poordad and colleagues randomly assigned 50 HCV genotype 1-infected adult patients (82% men; 34% black; 84% genotype 1a) without cirrhosis who previously failed DAA therapy to receive one of three once-daily treatment regimens.
Group A received 200 mg glecaprevir plus 80 mg pibrentasvir, group B received 300 mg glecaprevir plus 120 mg pibrentasvir with 800 mg ribavirin, and group C received 300 mg glecaprevir plus 120 mg pibrentasvir without ribavirin. Group A enrollment was halted at six patients to optimize dosing.
Intent-to-treat analysis showed 92% (95% CI, 81-97) of all patients achieved SVR at 12 weeks. Further, 100% (95% CI, 61-100) of the six patients in group A achieved SVR12, compared with 95% (95% CI, 78-99) of the 22 patients in group B and 86% (95% CI, 67-95) of the 22 patients in group C.
No patients in group A experienced virologic failure, compared with one patient in group B and one patient in group C.
Most adverse events, which occurred in 84% of patients, were mild and most commonly included headache, fatigue, nausea and insomnia.
“Such events were more common in the [ribavirin]-containing arm,” investigators wrote.
Further, no serious adverse events related to the study drug were reported, and the researchers observed no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin or hemoglobin.
“The combination of glecaprevir and pibrentasvir showed potent antiviral activity, regardless of the presence of one or more baseline resistance-associated polymorphisms, and irrespective of previous DAA-containing treatment regimens, resulting in high SVR12 rates in non-cirrhotic patients with HCV GT1 infection,” Poordad and colleagues concluded. “This suggests the combination … is highly effective in this population which, currently, has limited treatment options.” – by Adam Leitenberger
Disclosures: This trial was funded by AbbVie. Poordad reports he has received grants and research support from AbbVie, Achillion, Anadys, Biolex, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Idera, Intercept, Janssen, Medarex, Medtronic, Merck, Novartis, Santaris, Scynexis, Vertex and ZymoGenetics. He also reports he is a speaker for Gilead, Kadmon, Merck, Onyx/Bayer, Genentech, GlaxoSmithKline, Salix and Vertex, and is a consultant/advisor for AbbVie, Achillion, Anadys, Biolex, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Intercept, Merck, Novartis, Tibotec/Janssen, Theravance and Vertex. Please see the full study for a list of all other researchers’ relevant financial disclosures.