BOSTON, MA—A fixed-dose combination of pangenotypic direct-acting antivirals was “highly effective” in treatment-naïve patients with hepatitis C virus (HCV) genotypes (GT) 1, 2, and 3, a study presented at The Liver Meeting® 2016 has shown.
The “MK3” therapy is a three-drug regimen formulated into a fixed-dose combination tablet. These are MK-3682, an NS5B uridine nucleotide polymerase inhibitor (225mg per tablet); grazoprevir (MK-5172), an NS3/4A protease inhibitor (50mg per tablet); and ruzasvir (MK-8408), a next-generation NS5A inhibitor (30mg per tablet). The regimen is given as two tablets, once daily, without regard to food.
Eric Lawitz, MD, of the Texas Liver Institute, University of Texas Health Science Center, in San Antonio, TX, and colleagues evaluated this regimen, using either the fixed dose combination tablets or individual components, both with and without ribavirin (RBV), in the C-CREST 1&2 studies in 664 patients with GT1 (n=176; 51 were GT1a and 49, GT1b), 2 (n=151), or 3 (n=337) infection.
Patients with or without compensated cirrhosis were included in each group. GT1- and GT2-infected patients were treatment-naïve but the GT3 cohort included patients who were both treatment-naïve or had been treated with pegylated interferon/RBV.
Results showed that MK3 for 8 or 12 weeks was highly effective in GT1 patients, with an SVR12 of 97%. Among GT2 patients, SVR12 was 98% after treatment with 12 or 16 weeks and, among GT3 patients, SVR12 was 96% following treatment for 8, 12, or 16 weeks.
Dr. Lawitz said that the addition of ribavirin did not increase SVR12 in either the GT2 or GT3 patients.
Among those with GT3 who were treatment-experienced with cirrhosis, SVR12 was 99%.
Relapses occurred at 8 weeks in the GT1a group (2 patients), GT1b group (1 patient), GT2 group (7 patients) and GT3 group (4 patients). In the GT3 patients, there were also 3 relapses at 12 weeks and 2 at 16 weeks. Among these, only 1 GT2 patient in the 8-week treatment group with RBV discontinued at day 5 due to drug-related adverse events (AEs) of fatigue and malaise.
Fatigue, headache, and nausea were the most frequent drug-related AEs. One patient with GT1 infection died from bacterial sepsis, a death determined to be unrelated to study drugs.
Study authors included employees at Merck and author disclosures included advisory committee and review panel membership at, and research support from, numerous other drug companies, including AbbVie, Achillion Pharmaceuticals, Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Novartis, and Gilead.