乌鸦传媒

SAN FRANCISCO -- An 8-week course of glecaprevir/pibrentasvir (Mavyret) was highly effective in treatment-naive patients with hepatitis C virus (HCV) genotypes 1,2, 4, and 6 infection with compensated cirrhosis, with no reported virologic failures, a researcher said here.

In an open-label, phase IIIb trial, sustained virologic response (SVR) rate at week 12 was close to perfect -- 100% in a per-protocol analysis and 98% in an intention-to-treat analysis, reported Robert S. Brown Jr., MD, of Weill Cornell Medical College in New York City.

An 8-week duration of glecaprevir/pibrentasvir is approved for treatment-naive patients with HCV genotypes 1-6 without cirrhosis, Brown noted in a presentation at the annual Liver Meeting, sponsored by the American Association for the Study of Liver Diseases (AASLD).

But registrational clinical trials showed that a 12-week course of treatment yielded a 99% SVR12 rate in treatment-naive patients with compensated cirrhosis, he added.

However, the 8-week course of the therapy had not yet been studied in treatment-naive patients with compensated cirrhosis, which is what the ongoing EXPEDITION-8 trial aimed to investigate.

Researchers enrolled 280 treatment-naive patients with HCV genotypes 1, 2, 4, and 6, but not genotype 3, to start. Brown said that "based on data emerging from ENDURANCE-3 and other studies, a second group was added of HCV genotype 3 treatment-naive patients, with anticipated enrollment of 60 subjects."

Treatment-naive adults were eligible for inclusion if they had HCV genotypes 1, 2, 4, or 6 and cirrhosis, which was defined as both a FibroTest ≥0.75 and APRI ≥2. Any discordant results required FibroScan ≥14.6 kPA, or biopsy showing cirrhosis. Patients also had to have a Child-Pugh score ≤6, and any patients with hepatocellular carcinoma, hepatitis B, HIV, or past or current evidence of decompensated cirrhosis were excluded.

Median patient age was 60, 60% were men, and 80% were white. The majority had HCV genotype 1 infection, about a quarter had history of injection drug use, and about a third had NS5A polymorphisms at baseline, Brown said.

He explained there were seven patients excluded from the per-protocol analysis, six of whom were deemed "treatment failures," though there were no virological failures reported.

Less than half of patients reported adverse events, and there were six serious adverse events reported, including duodenal ulcer hemorrhage, pyelonephritis, and atrial fibrillation. None of these were drug-related, and there were no adverse events leading to drug discontinuation. Moreover, there were no liver-related toxicities or cases of drug-induced liver injury, the authors said.

Given that there were no new safety signals and no virologic failures, Brown said that these results supported an 8-week duration of glecaprevir/pibrentasvir for this population.

AASLD session moderator Norah Terrault, MD, of the University of California San Francisco, asked if there was any information on patients missing doses, to give a sense of how robust the treatment would be if doses were missed in a cirrhotic population.

Brown said that assessment was "limited to pill counts," and added that one patient who was not included in the per-protocol analysis, and stopped their treatment early, was in week 7.

"We've seen increasing data that these regimens do have more robustness than we think. But the shorter you go, the more you fret about it," he said.

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