Phase III Trial: 8-Week Bemnifosbuvir/Ruzasvir Regimen Matches Standard Hepatitis C Therapy
Atea Pharmaceuticals has announced that its investigational once-daily oral combination of bemnifosbuvir and ruzasvir met the primary endpoint in a Phase III clinical trial for chronic hepatitis C.The 8-week treatment regimen demonstrated non-inferiority to the standard 12-week sofosbuvir/velpatasvir (Epclusa) regimen in achieving sustained virologic response (SVR), the key measure of hepatitis C cure.The findings suggest that the shorter regimen could provide an effective, more convenient treatment option for eligible patients, pending regulatory review and approval.
BEM/RZR demonstrated statistical non-inferiority compared to the fixed-dose combination of sofosbuvir and velpatasvir (SOF/VEL) in the modified intent-to-treat (mITT) population, achieving the trial’s primary endpoint. C-BEYOND enrolled patients reflective of the current real-world population living with HCV in the US and Canada.
In the mITT analysis (n=905, cirrhotic and non-cirrhotic), BEM/RZR achieved a 93.9% sustained virologic response (SVR) rate vs. 94.8% for SOF/VEL (Epclusa) at Week 24, encompassing SVR at 12 weeks post-treatment (accepted definition of cure for HCV) in both arms. These results achieved the primary endpoint of statistical non-inferiority, with a 95% confidence interval for difference in SVR rates within the prespecified 5% margin. The mITT analysis in patients without cirrhosis (n=721) showed BEM/RZR (8 weeks of treatment) achieved a 93.5% SVR rate vs. 94.6% for SOF/VEL (12 weeks of treatment). In patients with cirrhosis (12 weeks treatment in both arms) (n=184), BEM/RZR achieved a 95.4% SVR rate vs. 95.4% for SOF/VEL. In C-BEYOND, rates of virologic failure across all populations were low and comparable between treatment arms. Statistical non-inferiority was also met in secondary endpoints, including the per-protocol analysis.
"We are pleased to announce these positive results from C-BEYOND showing our regimen of BEM/RZR achieved high cure rates across all populations and genotypes,” said Jean-Pierre Sommadossi, PhD, Founder and Chief Executive Officer of Atea Pharmaceuticals. “As today is World Hepatitis Day, it underscores that HCV presents complex public health challenges. We believe the profile of our regimen will substantially contribute to the World Health Organization’s goal of HCV eradication. We look forward to sharing results from C-FORWARD, Atea’s second Phase 3 trial of BEM/RZR outside North America, in early 2027, and to bringing BEM/RZR to patients as soon as possible.”
"Achieving these high cure rates with just 8 weeks of BEM/RZR in patients without cirrhosis, alongside a favorable drug-drug interaction profile and the flexibility to be taken with or without food, is a meaningful step forward for HCV care. A shorter, simpler regimen has the potential to streamline prescribing decisions and accelerate the test-and-treat strategies that are essential to HCV elimination," said Eric Lawitz, MD, Clinical Professor of Medicine at UT Health San Antonio and the Texas Liver Institute. "Many of the patients I see in my practice are managing multiple chronic conditions, taking several concomitant medications, and navigating real barriers to consistent follow-up. Those realities are exactly why we need HCV regimens that are highly effective, convenient to administer and compatible with the medications patients are already taking every day."
BEM/RZR was administered as an 8-week regimen to patients without cirrhosis compared with the 12-week regimen of SOF/VEL, highlighting the potential of BEM/RZR to deliver robust antiviral efficacy with a shorter treatment duration. In the US, approximately 80-90% of people living with HCV do not have cirrhosis. Together with its potential advantages of a shorter treatment duration for most patients, low risk of drug-drug interactions and no food effect, the results from C-BEYOND further reinforce BEM/RZR’s potential as a differentiated, best-in-class treatment option for people with HCV.
Chronic HCV infection remains an ongoing public health crisis. If left untreated, HCV can progress to cirrhosis, end-stage liver disease and liver cancer, and it remains one of the leading causes of liver cancer in the US, Europe and Japan. Approximately 50 million people worldwide are living with HCV, including up to 4 million people in the US, while new diagnoses continue to outpace annual cures. Additionally, many people living with HCV are also managing other chronic conditions, and roughly 80% take multiple concomitant medications for common comorbidities such as heartburn, heart arrhythmia, high blood pressure and gastroesophageal reflux disease (GERD), which may increase the potential for drug-drug interactions with currently approved therapies.
In C-BEYOND, BEM/RZR demonstrated robust SVR rates across HCV genotypes that predominate in North America. C-FORWARD, which is being conducted outside North America, includes a broader range of HCV genotypes and is expected to provide additional efficacy data in genotypes more frequently found outside the US and Canada. In C-BEYOND, BEM/RZR was generally safe and well tolerated with no drug-related serious adverse events or drug related early treatment discontinuations. Safety was comparable between treatment arms.
“We are grateful to the patients and clinicians who participated in the C-BEYOND study, whose engagement and support made this important progress possible in the first-ever successful head-to-head trial in a global Phase 3 HCV program,” said Janet Hammond, MD, PhD, Chief Development Officer of Atea Pharmaceuticals. “These strong results underscore the promise of BEM/RZR for the treatment of patients infected with HCV. Looking ahead, we believe C-FORWARD will provide important additional insight into the regimen’s efficacy across HCV genotypes which are less common in the US and Canada, and further our goal of bringing a simplified, effective HCV treatment option to patients worldwide.”
C-BEYOND was conducted at approximately 120 sites in the US and Canada. C-FORWARD, which is fully enrolled with more than 880 patients, is being conducted at approximately 120 sites in 17 countries outside North America and is on track to report topline results in early 2027. Atea plans to present the detailed results of its global Phase 3 program in HCV at future medical conferences and submit to peer-reviewed medical journals for publication.
About the C-BEYOND and C-FORWARD Phase 3 Trials in Adults with Chronic HCV
The global Phase 3 program is evaluating the fixed-dose combination (FDC) of BEM/RZR for the treatment of chronic HCV in patients with and without compensated cirrhosis. The program consists of two open-label controlled trials: C-BEYOND in North America and C-FORWARD outside North America. C-BEYOND (NCT06868264) enrolled 905 (mITT population) treatment-naïve patients, while C-FORWARD (NCT07037277) has enrolled more than 880 treatment-naïve patients. The trials compare the FDC regimen of BEM, a nucleotide analog polymerase inhibitor, and RZR, an NS5A inhibitor, to the FDC regimen of SOF/VEL. The regimen of BEM/RZR is administered orally once daily for eight weeks (in patients without cirrhosis) or 12 weeks (in patients with compensated cirrhosis), while the regimen of SOF/VEL is administered orally once daily for 12 weeks to all patients, with or without compensated cirrhosis.
The primary endpoint for each trial is HCV RNA below the 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. SVR12 is the accepted definition of cure for HCV. Measurement at 24 weeks from the start of treatment is to ensure the primary endpoint measurement occurs at the same relative timepoint from the start of treatment in all patients. The primary endpoint was assessed in the mITT population in C-BEYOND, which is comprised of all patients who received at least one dose of the regimen and includes patients who discontinued early, were not compliant or were lost to follow-up. The mITT analysis is the agreed upon primary endpoint with the United States Food and Drug Administration (FDA).
