Pooled Data Back Short-Course HCV Tx

A short-course treatment of glecaprevir-pibrentasvir (Mavyret) was efficacious and well tolerated in treatment-naive patients with all hepatitis C virus (HCV) genotype infections with or without cirrhosis, international researchers reported.

In a post-hoc analysis from eight pooled trials involving over 2,300 patients, treatment with glecaprevir-pibrentasvir led to sustained viral response (SVR) rates of 97.6% at 12 weeks in an intent-to-treat population (ITT) and 99.3% in a modified ITT population, regardless of cirrhotic status, Eli Zuckerman, MD, of Carmel Medical Center Liver Institute in Haifa, Israel, and colleagues reported.

“These high SVR12 rates support the product labeling that recommends the use of glecaprevir/pibrentasvir for 8 weeks in treatment-naive HCV patients without cirrhosis or with compensated cirrhosis, regardless of genotype,” the group wrote online in Clinical Gastroenterology and Hepatology.

Glecaprevir-pibrentasvir is the only FDA-approved 8-week pangenotypic therapy available for treatment-naive chronic HCV patients irrespective of cirrhosis status, according to the authors. It therefore meets the needs of a diverse and changing HCV patient population and may reduce treatment costs.

“Treatment-naive patients currently comprise the majority of patients infected with HCV,” Zuckerman told MedPage Today. “Short treatment duration may assist in improving patient adherence, reducing treatment burden, and reaching elimination targets.”

The researchers explained that direct-acting antiviral therapy was initially prioritized for patients with more advanced liver disease or those who had previously failed interferon-based treatment. But with the rising incidence of infection among young people, especially drug users, the HCV patient population has rapidly shifted to treatment-naive individuals without cirrhosis who more often may be treated in the community setting.

“This study provides confidence that 8 weeks of glecaprevir-pibrentasvir is effective for patients with compensated cirrhosis,” said Andrew Muir, MD, MHS, of Duke University in Durham, North Carolina, noting that glecaprevir-pibrentasvir was initially approved as an 8-week course only if no cirrhosis was present and as a 12-week course if cirrhosis was present.

“It has ultimately been determined that only 8 weeks’ treatment is needed even if the patient has compensated cirrhosis,” said Muir, who was not involved in the study. “Nice to have this shorter duration of treatment.”

Study Details

The eight studies included previously published phase IIb, IIIa, and IIIb clinical trials, with patients randomized or assigned to receive 8 weeks of oral, once-daily glecaprevir-pibrentasvir (300 mg/120 mg). The enrolled populations were diverse, including patients with HCV and HIV-1 coinfection, all stages of chronic kidney disease, and a history of injection-drug use.

The post-hoc analysis of the genotype (GT) 1-6 dataset included 1,248 patients in the ITT group, of whom 73% were non-cirrhotic and 27% had compensated cirrhosis. About 85% of patients were younger than 65 years (median 54 years) and 80% were white. Most had GT1 (47%) or GT3 (22%).

The GT∆3CC dataset comprised 1,185 patients in the ITT population and their demographic characteristics were consistent with those in the GT1-6 group. Non-virologic failure was reported in 22 and 21 patients in the GT1-6 and GT∆3CC datasets, respectively, translating to modified ITT populations of 1,226 and 1,164 patients, respectively.

Eight virologic failures, seven in patients without cirrhosis and one in a patient with cirrhosis, occurred in the ITT population. These failures were not associated with markers of advanced liver disease or populations of interest, such as those with current alcohol use, opioid substitution therapy, a history of injection-drug use, and severe renal impairment.

Tolerability was acceptable, with treatment-emergent adverse events (AEs) occurring in 58% of patients, the most frequent being headache and fatigue (12% each). Serious AEs and those necessitating glecaprevir-pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively.

Among study limitations, the authors acknowledged that the post-hoc analysis lacked the statistical power to compare patient groups, and not all studies reported the same data or fully captured data on injection-drug use. A further limitation was the low number of patients in some subgroups — for example, those with recent injection-drug use and those with HCV genotype 5.