Bemnifosbuvir, Ruzasvir Combination Shows 97% SVR12 Rate in Phase 2 Trial for HCV

Atea Pharmaceuticals has announced new data from the lead-in cohort of an ongoing phase 2 combination study of bemnifosbuvir and ruzasvir for the treatment of hepatitis C virus (HCV).¹

Results were presented at the European Association for the Study of the Liver (EASL) Congress in Milan, Italy, and showed an 8-week treatment regimen with combination bemnifosbuvir and ruzasvir had a 97% sustained virologic response (SVR) rate in a cohort of patients without cirrhosis at 12 weeks post-treatment.¹

“I am excited about the initial bemnifosbuvir and ruzasvir combination data. The combination of a short 8-week treatment duration, a low risk of drug-drug interactions, and robust antiviral efficacy across all genotypes makes this an attractive regimen,” Eric Lawitz, MD, medical director of the Texas Liver Institute and a clinical professor of medicine at the University of Texas Health Science Center, said in a press release.¹

Globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring per year. The World Health Organization recommends therapy with pan-genotypic direct-acting antivirals (DAAs) for all adults, adolescents, and children down to 3 years of age with HCV.² Most existing treatment regimens have a 12 - 24 week duration, but combination bemnifosbuvir and ruzasvir has shown high antiviral potency, short treatment duration, low risk of drug interaction, and a high barrier to resistance, making it a promising potential new HCV treatment regimen.¹

An oral, purine nucleotide prodrug, bemnifosbuvir is designed to inhibit viral replication by impairing viral RNA polymerase, a key component in the replication machinery of enveloped positive single-stranded RNA viruses. It is being developed in combination with ruzasvir, an oral NS5A inhibitor, for the treatment of HCV.¹

As single agents, both bemnifosbuvir and ruzasvir have demonstrated potent pan-genotypic antiviral activity against HCV. Combined together, they have exhibited synergistic in vitro activity against HCV with no pharmacokinetic drug-drug interactions in healthy volunteers.¹

The safety and efficacy of 8 weeks of treatment combination once-daily bemnifosbuvir 550 mg and ruzasvir 180 mg are being evaluated in a global phase 2 clinical trial involving treatment-naïve, chronic HCV-infected patients either without cirrhosis or with compensated cirrhosis. According to a release from Atea, approximately 280 treatment-naïve patients across all HCV genotypes, including the lead-in cohort of 60 patients without cirrhosis, are expected to be enrolled in this phase 2 trial and topline results from all patients are anticipated in the second half of 2024.¹

Primary endpoints include safety and SVR at 12 weeks post-treatment (SVR12). Other virologic endpoints include virologic failure, SVR at 24 weeks post-treatment (SVR24), and resistance.¹

In total, the lead-in cohort included 60 patients who were predominantly male (57%), Caucasian (95%), and infected with genotype 1 (75%). Results from the lead-in cohort of the phase 2 study showed a 97% SVR12 rate. Of note, the SVR12 rate in participants infected with HCV genotype 3 (n = 13), a historically difficult-to-treat genotype of HCV, was 100%. Investigators noted the combination regimen was well tolerated, with no drug-related severe adverse events or treatment discontinuations.¹

“Today, new challenges are hindering progress towards our goal of HCV elimination in the U.S. and globally. Patient demographics have changed, and the pace of new HCV infections is quickly outpacing the rate of those being treated. It is apparent that further innovations are required to address the needs of today’s HCV-infected patients,” Jean-Pierre Sommadossi, PhD, chief executive officer and founder of Atea Pharmaceuticals, said in a press release.¹ “The data being presented at EASL demonstrate a potential best-in-class profile that combines the most compelling attributes of current HCV drug treatments through the innovative combination of bemnifosbuvir and ruzasvir. We look forward to reporting the full results from our ongoing Phase 2 study during the second half of this year.”

References:

1. ^{Atea Pharmaceuticals. Atea Pharmaceuticals Presents Positive Initial Phase 2 Data for Bemnifosbuvir and Ruzasvir Combination for Treatment of Hepatitis C Virus at EASL Congress 2024. Investor Relations. June 5, 2024. Accessed June 6, 2024. https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-presents-positive-initial-phase-2-data}
2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed June 6, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}