TOPLINE

An 8-week, once-daily regimen of bemnifosbuvir and ruzasvir led to a sustained virologic response at 12 weeks (SVR12) in 98% of adherent, treatment-naive patients with chronic hepatitis C in a phase 2 trial. The response rate was 99% in adherent patients without cirrhosis and 88% in those with compensated cirrhosis. The regimen was well tolerated, with no serious adverse events attributed to either drug.

METHODOLOGY

• Direct-acting antivirals have transformed hepatitis C care, but glecaprevir-pibrentasvir, the only approved regimen that is effective against all major genotypes and has an 8-week treatment duration, can interact with other medicines and must be taken with food.
• Researchers conducted a phase 2 clinical trial in 13 countries to test whether an 8-week, once-daily combination of bemnifosbuvir and ruzasvir, which targets the hepatitis C virus through two different proteins, was effective in 275 adults with chronic infection, with or without compensated cirrhosis, who were naive to treatment (mean age, 50 years; 52% men). 
• Patients took 550 mg of bemnifosbuvir (two 275-mg tablets) and 180 mg of ruzasvir (two 90-mg capsules) once daily for 8 weeks, with or without food. Efficacy was then evaluated in three overlapping populations: all 275 treated patients, 259 patients with 12-week outcomes regardless of adherence, and 215 patients who took at least 90% of doses, with adherence confirmed using pill counts and plasma drug levels.
• Treatment response was tracked by measuring the concentration of hepatitis C virus RNA in the blood. Genotypes of the virus were identified, and viral sequencing was performed at baseline and in cases of treatment failure to identify resistance mutations.
• The primary outcome was SVR12 in patients who took at least 90% of their doses; safety was assessed during treatment and for 4 weeks afterward.

TAKEAWAY

• SVR12 was achieved by 98% of adherent patients who took at least 90% of their doses, 95% of patients with 12-week outcomes regardless of adherence, and 90% of all treated patients. Virologic failure occurred in 14 patients (5%) in the all-treated group, and most failures were attributed to nonadherence.
• Among adherent patients without cirrhosis, SVR12 was 99.4%, with rates ranging from 99% to 100% across genotypes 1-4. Among adherent patients with compensated cirrhosis, SVR12 was 88.2%, with rates ranging from 80% to 90% depending on the genotype. 
• Among adherent patients, five (2%) experienced relapse within 4 weeks of finishing treatment, of whom one had no cirrhosis and four had compensated cirrhosis; 3 of the 4 patients with cirrhosis had developed new drug-resistance mutations by the time the virus rebounded. No one in this group experienced relapse between weeks 12 and 24; therefore, the 98% response rate persisted at 24 weeks.
• The regimen was well tolerated; 43% of the patients had at least one adverse event, most of which were mild to moderate, and no serious adverse events were judged to be related to the drugs.

IN PRACTICE

"[T]reatment duration was the critical factor underlying virologic failure in cirrhotic patients, and therefore extension of treatment duration may enhance efficacy," the authors wrote.

SOURCE

The study was led by Alina Jucov of the Arensia Exploratory Medicine GmbH, Chisinau, Moldova. It was published online in Hepatology.

LIMITATIONS

This was a single-arm study without a comparison group. Patients with hepatitis C often have difficulty staying on treatment and remaining in follow-up, particularly those with substance use or psychiatric conditions. Few patients had genotypes other than 1 and 3, potentially limiting the generalizability of the findings. The sample was too small to compare outcomes based on history of drug use.

DISCLOSURES

This study was funded by Atea Pharmaceuticals, Inc. Five authors declared being employees and/or shareholders of Atea Pharmaceuticals, Inc. Multiple authors reported receiving consulting fees, speaker fees, research grants, or advisory fees from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.