Model predicts combo therapy may cure hepatitis C in 2 months
Oral treatment duo being tested in adults in 2 parallel clinical trials
New modeling data predict that bemnifosbuvir and ruzasvir, an experimental combination treatment being developed by Atea Pharmaceuticals for chronic hepatitis C, may be able to cure the viral infection within two months.
“The new multiscale modeling data … showed our regimen simultaneously disrupts intracellular [within-cell] replication and blocks the assembly and release of new HCV [hepatitis C viruses] … into the bloodstream,” Jean-Pierre Sommadossi, PhD, Atea’s CEO and founder, said in an emailed statement to Liver Disease News.
“The model’s projection of a potential seven- to eight-week cure further reinforces the promise of bemnifosbuvir and ruzasvir as a highly effective, short-duration therapy,” Sommadossi said.
These and other data — all supporting the combo’s potential to be an effective and convenient treatment for chronic hepatitis C — were shared by the company earlier this month at the annual The Liver Meeting of the American Association for the Study of Liver Diseases.
The new findings “reinforce the differentiated profile of our fixed-dose combination regimen of bemnifosbuvir and ruzasvir as a potent, pan-genotypic and convenient regimen with the potential to transform the treatment landscape and bring us closer to eradication of HCV,” Sommadossi said in a company press release. Pan-genotypic therapies are those effective against all major genetic subtypes of a specific virus, in this case, the HCV.
Atea’s fixed-dose combination tablet, containing both the antiviral treatments bemnifosbuvir and ruzasvir, is being tested against the approved therapy Epclusa (sofosbuvir/velpatasvir) in adults with chronic hepatitis within two parallel Phase 3 clinical trials.
One trial, C-BEYOND (NCT06868264), is enrolling participants at sites in the U.S. and Canada. The other, C-FORWARD (NCT07037277), is recruiting patients at sites in Moldova, South Africa, and South Korea. A total of more than 1,700 participants are expected to be recruited.
Rates of new hepatitis C infections now outpace cures
HCV, which is spread by contact with infected blood, infects the liver, leading to liver inflammation or hepatitis. There are available treatments for hepatitis C that can usually cure the infection, but globally, rates of new infections occur more quickly than cures. Therefore, hepatitis C remains a persistent health problem worldwide.
The bemnifosbuvir plus ruzasvir combo is designed to stop HCV from multiplying within the body’s cells. In principle, these therapies work similarly to available hepatitis C treatments, but Atea expects them to work faster, which could offer more convenience for patients.
A previous Phase 2 trial (NCT05904470), now completed, tested the therapy combo — taken for eight weeks, or about two months — in 275 people with chronic hepatitis C who had not previously received treatment.
The results showed that 98% of participants who took the medications as instructed achieved 12-week sustained virologic responses, meaning HCV was not detectable three months after completing treatment. When those who didn’t take the meds exactly as directed were also included, the response rate was 95%.
Model shows consistent benefits, regardless of liver scarring, genetics
In a new analysis, researchers used data from the Phase 2 study to model how the combination treatment affects HCV within the body. These data indicated that the therapy blocked both viral replication and the assembly of new viruses, with consistent effects seen regardless of HCV genetic subtype or the extent of liver scarring.
The model predicted that bemnifosbuvir and ruzasvir would lead to an HCV cure within about eight weeks for patients who don’t have cirrhosis, or irreversible liver scarring. For individuals with cirrhosis, the model predicted that curative treatment would take up to a month longer.
Our regimen of bemnifosbuvir and ruzasvir has a high barrier to resistance and remains effective even in patients with [starting] resistance.
At the meeting, the company also presented findings regarding HCV’s ability to develop resistance to the combination treatment — a concern with antiviral therapies.
By analyzing Phase 2 trial data, Atea found that, in seven of the 14 cases where the combo did not cure the infection, the patients had viruses containing mutations that could provide resistance at the study’s start. However, most cases of treatment failure — 64.3% or nearly two-thirds — were found to be due to the treatment not being taken as directed.
“Our regimen of bemnifosbuvir and ruzasvir has a high barrier to resistance and remains effective even in patients with [starting] resistance, which is critical to validating that the few viral failures observed in the Phase 2 trial were principally due to nonadherence rather than resistance to therapy,” Sommadossi said in the statement to Liver Disease News.
Data also show combo therapy can be taken alongside meds for stomach acid
Additionally at the meeting, the company presented pharmacological data from a Phase 1 trial (NCT06204679) that tested the fixed-dose combination tablet of bemnifosbuvir and ruzasvir in healthy adults. Those results showed that the experimental combo can be taken without regard to food, as well as alongside famotidine, a medication that can affect the efficacy of certain antiviral medications.
Famotidine, sold under the name Pepcid among others, is used to reduce stomach acid.
“Our market research indicates that as many as 80% of U.S. HCV patients take medications for other conditions, including famotidine, which has historically reduced the effectiveness of certain other HCV antivirals,” Sommadossi said. “The Phase 1 data we presented highlight the optimized, differentiated profile of our regimen, including its compatibility with famotidine and its convenience with no food effect, both of which may help to support real-world adherence and address the needs of today’s HCV patients.”
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