Bemnifosbuvir, Ruzasvir Regimen Meets Safety, SVR Primary Endpoints in Phase 2 HCV Trial

Eric Lawitz, MD

Credit: UT Health San Antonio

Atea Pharmaceuticals has announced positive results from its phase 2 study of an 8-week bemnifosbuvir and ruzasvir regimen for the treatment of hepatitis C virus (HCV), with the trial meeting its primary endpoints for safety and sustained virologic response at 12 weeks post-treatment (SVR12).^1,2

According to a December 4, 2024, press release from Atea, primary endpoint results demonstrated a 98% SVR12 rate in the per-protocol treatment adherent patient population after 8 weeks of treatment with the bemnifosbuvir and ruzasvir regimen, which was generally safe and well-tolerated with no drug-related serious adverse events or treatment discontinuations.^1,2

The company plans to present full data from the phase 2 study at a scientific meeting during the first half of 2025 and is currently preparing for the phase 3 program, which is expected to follow an End of Phase 2 meeting with the US Food and Drug Administration anticipated for early 2025.¹

“I’ve experienced first-hand the changing population of HCV patients and the increasing importance of short duration therapy,” Eric Lawitz, MD, The Texas Liver Institute, clinical professor of medicine at the University of Texas Health San Antonio, said in a press release.¹ “Our current HCV patients are younger, and frequently taking concurrent medications for their comorbidities. More recently, there are also fewer patients presenting with cirrhosis. I’m encouraged by these promising Phase 2 results and look forward to the Phase 3 program.”

A nucleotide analog polymerase inhibitor, bemnifosbuvir has been shown in in vitro studies to be approximately 10-fold more active than sofosbuvir against a panel of laboratory strains and clinical isolates of HCV genotypes 1–5, with bemnifosbuvir additionally remaining fully active against sofosbuvir resistance-associated substitutions (S282T), with up to 58-fold more potency than sofosbuvir.¹

An NS5A inhibitor, ruzasvir has demonstrated highly potent and pan-genotypic antiviral activity in preclinical and clinical studies. It has been administered to more than 1500 HCV-infected patients at daily doses of up to 180 mg for 12 weeks and has demonstrated a favorable safety profile. The pharmacokinetic profile of both bemnifosbuvir and ruzasvir supports once-daily dosing.¹

The global phase 2 study of a bemnifosbuvir and ruzasvir regimen enrolled 275 treatment-naïve patients, both with and without compensated cirrhosis. It was designed to evaluate the safety and efficacy of 8 weeks of treatment with the regimen consisting of once-daily bemnifosbuvir 550 mg and ruzasvir 180 mg.¹

The study’s primary endpoints include safety and SVR12 in the per-protocol treatment adherent population, while secondary and other endpoints include SVR12 in the per-protocol population regardless of treatment adherence, virologic failure, and resistance.¹

Results showed a 98% (208/213) SVR12 rate in the per-protocol treatment adherent patient population after 8 weeks of treatment with a regimen of bemnifosbuvir and ruzasvir. In the efficacy evaluable patient population, which included 17% treatment non-adherent patients, a 95% (242/256) SVR12 rate was achieved.¹

Of note, 99% (178/179) of treatment adherent patients who were noncirrhotic and infected with genotypes 1-4 achieved SVR12, demonstrating robust pan-genotypic potency and supporting an 8-week treatment in the phase 3 program. Treatment adherent patients with cirrhosis achieved a 88% (30/34) SVR12 rate. Viral kinetics were slower in these patients, but investigators noted all patients achieved 100% end-of-treatment response. In order to maximize efficacy, treatment duration in patients with cirrhosis will be 12 weeks in the phase 3 program.¹

Additionally, the regimen was generally safe and well-tolerated with no drug-related serious adverse events or treatment discontinuations.¹

“These high SVR12 results with only eight weeks of treatment with our regimen are extremely exciting and very significant given the unmet needs for today’s HCV patients. We are eager to discuss our program with regulators, including the US Food and Drug Administration, to promptly advance to Phase 3 development early next year,” Jean-Pierre Sommadossi, PhD, chief executive officer and founder of Atea, said in a press release.¹ “The HCV market continues to be underserved, and HCV diagnoses in the US outpace treatment rates annually. Our regimen has a potential best-in-class profile that includes the key features for successfully treating today’s HCV patients including convenience, low risk for drug-drug interactions and short treatment duration. We believe that this regimen has the potential to play a major role in the eradication of HCV in the US.”

References

1. ^{Atea Pharmaceuticals. Atea Pharmaceuticals Announces Positive Results from Phase 2 Study of Bemnifosbuvir and Ruzasvir Regimen for Treatment of Hepatitis C Virus (HCV). December 4, 2024. Accessed December 4, 2024. https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-announces-positive-results-phase-2-study}
2. ^{Atea Pharmaceuticals. Topline Phase 2 Results with High SVR12 Rates Potential Best-in-Class Pan-Genotypic Regimen. December 4, 2024. Accessed December 4, 2024. https://ir.ateapharma.com/static-files/a756069b-274e-4edb-b64f-ce90aee8c504}