Investigational Combination Hepatitis C Therapy Demonstrates a 97% Sustained Virologic Response

At the ongoing The Liver Meeting in San Diego, Atea Pharmaceuticals has presented posters about the company’s investigational antiviral combination of bemnifosbuvir and ruzasvir, which is being studied for potential hepatitis C virus (HCV) treatment. In one of the posters, the combination therapy achieved a 97% sustained virologic response at 12 weeks post-treatment (SVR12) in a phase 2 lead-in cohort. According to the investigators, the analysis supports a short 8-week treatment with bemnifosbuvir and ruzasvir for chronic HCV.¹

A multiscale HCV viral kinetic model was utilized to estimate the clinical effectiveness of the combination of bemnifosbuvir and ruzasvir in blocking HCV replication and viral assembly/secretion against HCV. This model evaluated the combination of bemnifosbuvir and ruzasvir in the lead-in cohort (n=60) of a Phase 2 single-arm study. This cohort was comprised of treatment-naïve, non-cirrhotic patients with chronic HCV receiving 550 mg bemnifosbuvir once daily (QD) and 180 mg ruzasvir QD for 8 weeks. The multiscale model was fit to the plasma viral load (VL) and the alanine aminotransferase (ALT) data from all 60 subjects simultaneously through mixed-effects population fitting.¹

“A multiscale model of HCV infection and treatment was designed to estimate the in vivo effectiveness of agents including various combinations of direct-acting antivirals to block HCV replication and viral assembly,” Alan Perelson, PhD, senior fellow at Los Alamos National Laboratory, said in a statement. “The data presented today modeling the combination of bemnifosbuvir and ruzasvir for the treatment of HCV align with the reported clinical results from the lead-in cohort of the Phase 2 study. These data are highly encouraging.”²

The modeling results provided insight on the mechanism of action and demonstrated that the combination of bemnifosbuvir and ruzasvir was highly effective in blocking both viral replication and viral assembly/secretion in HCV-infected patients, independent of genotype, age, sex, or fibrosis score.¹

The Combination Therapy

According to the company, bemnifosbuvir has been shown in in vitro studies to be approximately 10-fold more active than sofosbuvir (SOF), against a panel of laboratory strains and clinical isolates of HCV GT 1–5. In vitro studies have also demonstrated bemnifosbuvir remained fully active against SOF resistance-associated substitutions (S282T), with up to 58-fold more potency than SOF.¹

The pharmacokinetic (PK) profile of bemnifosbuvir supports once-daily dosing for the treatment of HCV. Bemnifosbuvir has been shown to have a low risk for drug-drug interactions. Bemnifosbuvir has been administered to over 2,200 subjects and has been well-tolerated at doses up to 550 mg for durations up to 12 weeks in healthy subjects and patients.¹

The other half of the combination, ruzasvir, has demonstrated highly potent and pan-genotypic antiviral activity in preclinical (picomolar range) and clinical studies. Ruzasvir has been administered to over 1,500 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The PK profile of ruzasvir supports once-daily dosing.¹

Atea is a Boston-based, clinical-stage biopharmaceutical company engaged in the development of oral antiviral therapeutics for viral diseases. They also have an investigational COVID-19 therapy in clinical trials.

References

1.Ribeiro R. Multiscale Modeling of Lead-in Results from a Phase 2 Study of an 8-Week Combination Regimen of Bemnifosbuvir and Ruzasvir in Patients with Chronic Hepatitis C Virus Infection. Poster #1467 presented at The Liver Meeting. November 15-19, 2024. San Diego, CA.
2. Atea Pharmaceuticals Presents Multiple New Datasets Supporting the Combination of Bemnifosbuvir and Ruzasvir for the Treatment of Hepatitis C Virus at AASLD’s The Liver Meeting 2024. Atea Pharmaceuticals press release. November 15, 2024. Accessed November 19, 2024.
https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-presents-multiple-new-datasets-supporting