Antiviral treatment combo leads to sustained HCV clearance in trial
Bemnifosbuvir-ruzasvir combo now will be tested in upcoming Phase 3 trial
A two-month regimen of Atea Pharmaceuticals’ once-daily oral antiviral treatment for hepatitis C — a combination of bemnifosbuvir and ruzasvir — leads to sustained hepatitis C virus (HCV) clearance three months after the therapy’s completion.
That’s according to top-line data from the first group of 60 hepatitis C patients treated in an ongoing, fully-enrolled, global Phase 2 clinical trial (NCT05904470). Additional results from the more than 200 remaining trial participants are expected later this year.
None of the participants had decompensated cirrhosis, or permanent liver scarring that significantly affects the organ’s function, nor had received previous treatment.
“Bemnifosbuvir and ruzasvir data … demonstrate a potential best-in-class profile and the promise of this combination to address the unmet needs of today’s [HCV-infected] patient,” Jean-Pierre Sommadossi, PhD, CEO and founder of Atea, said in a company press release reporting latest financial results and business updates.
The company also announced that a fixed-dose combination tablet of bemnifosbuvir and ruzasvir has been selected for an upcoming Phase 3 program, and for subsequent commercialization in the event of regulatory approval.
Ongoing Phase 2 trial testing antiviral treatment combo in patients
In the trial, the selected tablet — which will reduce the daily number of pills needed from four to two — was shown to achieve blood levels “comparable to individually administered bemnifosbuvir and ruzasvir used in Phase 2 and other studies,” Atea stated.
HCV is the cause of hepatitis C, a common form of hepatitis, a term broadly referring to inflammation of the liver. While some HCV infections are acute and will clear on their own without major issues, chronic HCV infections can lead to serious liver injury. Patients may eventually develop cirrhosis, or irreversible liver scarring, and/or liver cancer.
A number of antiviral medications, called direct-acting antivirals, are available, and are usually recommended for managing HCV infections. In general, these treatments aim to disrupt the virus’ ability to multiply and infect other cells in the body.
However, in the U.S., according to Sommadossi, “the reported annual incidence of approximately 100,000 new chronic HCV infections is outpacing the number of people cured with direct-acting antivirals.”
“Many HCV patients take concomitant medications and in the wake of the opioid epidemic, people with substance abuse disorders and other populations with mental health disorders associated with poor medication adherence, are at the highest risk for HCV,” Sommadossi said.
[In the U.S.], the reported annual incidence of approximately 100,000 new chronic HCV infections is outpacing the number of people cured with direct-acting antivirals.
The Atea CEO also indicated that, to reach these populations effectively, there’s a strong need for therapies that don’t interact with other drugs and that require only a short treatment duration to be effective.
Bemnifosbuvir and ruzasvir work similarly to direct-acting antivirals, but together they are expected to be able to clear the virus more quickly, allowing a short treatment course. Data also indicates they have a low risk of interaction with other drugs.
Top-line data show 98% of patients had sustained treatment response
The ongoing Phase 2 study enrolled a total of 275 people with chronic HCV infection. The participants either had no cirrhosis or compensated cirrhosis, where the liver can still function despite extensive scarring, and had never used any antiviral therapies.
All those enrolled are being treated with a once-daily oral combination of bemnifosubvir, at 550 mg, and ruzasvir, at 180 mg, for eight weeks, or about two months.
In addition to safety, the study’s main goal is to assess how many patients achieve a sustained virologic response 12 weeks, or about three months, after treatment completion; this measure is dubbed SVR12. A virologic response is defined as an HCV load below the lower limit of detection.
At first, the study enrolled a lead-in group of 60 participants without cirrhosis. Initial results from that group showed that viral load was rapidly reduced upon treatment initiation, and all 60 people had HCV levels below the detectable limit by the end of the two-month treatment window.
Nearly all participants, 98%, achieved SVR four weeks after the treatment was completed. Based on those results, the trial continued recruitment for the remaining study participants.
Top-line data from the lead-in group, presented at a conference earlier this summer, showed that 97% of patients achieved SVR12, with virologic responses sustained for three months after stopping the therapy.
The two patients who failed to meet this main goal had low levels of the medication in the blood and there were no signs that the HCV virus had mutated to resist treatment. As such, Atea believes that their poor outcomes were due to a lack of treatment adherence, and not a general resistance of the virus to treatment.
Moreover, all of the 13 patients infected with genotype 3, an HCV strain that’s known to be particularly difficult to treat, achieved SVR12.
The combination therapy was well tolerated with no treatment-related serious adverse events or discontinuations, the data showed.
No additional details were provided about the planned Phase 3 trial.
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