Boston-based Atea Pharmaceuticals announced it had dosed the first patient for its C-BEYOND phase 3 trial in the US and Canada. The study will evaluate the regimen of bemnifosbuvir and ruzasvir for the treatment of adults with chronic hepatitis C virus (HCV) compared to the combination regimen of sofosbuvir and velpatasvir.1 “Dosing the first patient in our global phase 3 program is a major advancement as we work to deliver a differentiated, next-generation therapy for HCV,” Atea CEO Jean-Pierre Sommadossi, PhD, said in a statement.1
Study Parameters
Along with the C-BEYOND trial in the US and Canada, the company is conducting its C-FORWARD, an international trial. Each trial will enroll approximately 880 treatment-naïve patients, including those with and without compensated cirrhosis. 1
The regimen of bemnifosbuvir and ruzasvir will be administered orally once-daily for 8 weeks (in patients without cirrhosis) or 12 weeks (in patients with compensated cirrhosis) while the regimen of sofosbuvir and velpatasvir will be administered orally once-daily for 12 weeks for all patients with or without compensated cirrhosis. 1
The primary endpoint for each trial is HCV RNA < lower limit of quantitation (LLOQ) at 24 weeks from the start of treatment and encompasses sustained virologic response 12 weeks post-treatment (SVR12) in each arm. Measurement at 24 weeks from the start of treatment is to ensure the primary endpoint occurs at the same relative timepoint from the start of treatment in all patients. While C-BEYOND and C-FORWARD are both open-label trials, Atea has put measures and processes in place that are designed to blind Atea personnel to patient treatment assignments. 1
Phase 2 Data
At last year’sThe Liver Meeting, Atea presented a poster that demonstrated 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 supported a short 8-week treatment with bemnifosbuvir and ruzasvir for chronic HCV.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.2
What You Need to Know
Atea Pharmaceuticals has begun dosing patients in its Phase 3 C-BEYOND trial in the US and Canada, evaluating bemnifosbuvir and ruzasvir against the standard treatment of sofosbuvir and velpatasvir for chronic hepatitis C virus (HCV). A companion global trial, C-FORWARD, is being conducted outside North America.
The primary endpoint is achieving HCV RNA below the lower limit of quantitation at 24 weeks from treatment start.
In a phase 2 lead-in, the combo showed a 97% sustained virologic response (SVR12). Preclinical data indicate high potency, broad genotypic activity, and strong safety/tolerability.
About the Therapies
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
“We believe our regimen, which combines key features of short treatment duration, low risk for drug-drug interactions, and convenience with no food effect, if successfully developed, has best-in-class potential and the opportunity to improve patient outcomes and to expand the number of patients treated,” Sommadossi said.1
References
1. Atea Pharmaceuticals Announces Dosing of First Patient in C-BEYOND, Phase 3 Study Evaluating Regimen of Bemnifosbuvir and Ruzasvir for Treatment of Hepatitis C Virus. Atea Pharmaceuticals press release. April 9, 2025. Accessed April 9, 2025.
2. 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
