Bemnifosbuvir-ruzasvir combo clears HCV for most in Phase 2 trial
Top-line trial data show antivirals' promise as HCV treatment
A two-month course of an oral antiviral treatment combination of bemnifosbuvir and ruzasvir was well tolerated and led to sustained clearance of the hepatitis C virus (HCV) for most patients in a Phase 2 clinical trial.
Benefits were observed regardless of whether or not patients had cirrhosis, a complication of hepatitis C in which the liver is irreversibly scarred and damaged.
These recently announced top-line data from developer Atea Pharmaceuticals mean that the Phase 2 trial (NCT05904470) has met its main goals. Full findings are expected to be presented at a scientific meeting in the first half of 2025.
“These … results with only eight weeks of treatment with our regimen are extremely exciting and very significant given the unmet needs for today’s [hepatitis C] patients,” Jean-Pierre Sommadossi, PhD, CEO and founder of Atea, said in a company press release. “We are eager to discuss our program with regulators, including the U.S. Food and Drug Administration [FDA], to promptly advance to Phase 3 development early next year.”
The company expects to meet with the FDA to discuss these plans in early 2025. The Phase 3 program is expected to include two global studies that will compare the combination therapy to standard antiviral medication.
A faster HCV treatment
Both trials will use a fixed-dose combination tablet containing both bemnifosbuvir and ruzasvir, which is expected to enhance patient convenience by reducing the daily pill count from four to two.
Hepatitis C is a condition marked by liver inflammation, or hepatitis, due to an HCV infection. Some HCV infections clear up on their own without causing major damage, but others persist and can lead to serious liver issues such as cirrhosis, liver failure, and liver cancer.
There are a number of antiviral medications available for treating HCV infections, which generally work by suppressing the virus’ ability to grow and infect human cells.
Bemnifosbuvir and ruzasvir work similarly to these other medications, but together they’re expected to be able to clear the virus more quickly, enabling a shorter course of treatment. This might make the therapy more accessible to populations at a high risk of HCV, such as recreational drug users who are less likely to adhere to longer treatment.
Data also indicate that the treatment duo doesn’t interact with other medications patients might be using.
“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,” Sommadossi said.
Safety, response to treatment
The Phase 2 trial enrolled 275 people with chronic HCV infection who had never been treated with antivirals. Participants had either no cirrhosis or compensated cirrhosis, in which the liver can still function despite any damage that’s accrued.
All participants were treated with a once-daily oral combination of bemnifosubvir (550 mg) and ruzasvir (180 mg) for eight weeks.
The main goals were to assess the combination’s safety and the rate of 12-week sustained virologic responses (SVR12) among participants who followed the study’s established rules and adhered to the treatment regimen. SVR12 was defined as reaching an HCV level below the lower limit of quantification 12 weeks (three months) after treatment completion.
Previously reported results from a first group of 60 participants without cirrhosis showed that nearly all achieved SVR12, and that the treatment was well tolerated.
Now, top-line results from all study participants confirmed the combo’s favorable safety profile, with no treatment-related serious adverse events or treatment discontinuations.
Moreover, 98% of treatment-adherent participants — 208 of 213 people — achieved SVR12, meeting the study’s main efficacy goal. When looking at the 256 patients with evaluable efficacy data, 17% of whom did not adhere strictly to the treatment, 95% still achieved SVR12.
Of the 179 treatment-adherent patients without cirrhosis who were infected with any of four different strains of HCV, all but one reached SVR12, emphasizing the efficacy of the two-month regimen for several viral strains.
This main goal was also achieved by 88% of treatment-adherent patients with cirrhosis. The rate of HCV suppression was slower in patients with cirrhosis, but all still ultimately achieved viral clearance after the two-month treatment, according to Atea.
Based on these findings, patients with cirrhosis in future Phase 3 studies will receive a longer, three-month treatment regimen.
Atea believes the combination therapy is poised to better reach an evolving HCV-infected population, with patients now being younger, more likely to be using other medications, and less likely to have cirrhosis than in the past.
“I’ve experienced first-hand the changing population of HCV patients and the increasing importance of short duration therapy,” said Eric Lawitz, MD, vice president of scientific and research development at the Texas Liver Institute and a professor at the University of Texas Health San Antonio. “I’m encouraged by these promising Phase 2 results and look forward to the Phase 3 program.”
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