New hepatitis E treatment more potent than available drugs: Lab study
Developer planning human trial of AT-587 for HEV, to launch midyear
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In preclinical studies, AT-587, Atea Pharmaceuticals’ lead oral candidate for treating hepatitis E, showed potent antiviral activity against multiple strains of the hepatitis E virus (HEV) in lab-grown human liver cells, with no signs of toxicity.
Data also showed that the experimental therapy was more potent against HEV — including treatment-resistant strains — than the available medications sofosbuvir (sold as Sovaldi) and ribavirin (sold as Virazole, with generics available). These two antiviral drugs, approved for use in combination for hepatitis C, are often used off-label for treating hepatitis E.
According to the researchers, these new results show the promise of AT-587 as a potentially direct-acting treatment for hepatitis E.
“With no antivirals currently marketed for HEV, AT-587 has the potential to address a significant unmet need for a treatment option for patients with chronic HEV infection who [have weakened immune systems] or [are] at high risk for rapid progression to cirrhosis [irreversible liver scarring],” Jean-Pierre Sommadossi, PhD, CEO and founder of Atea, said in a company press release details the research findings.
The data were presented in a poster, titled “Discovery and Preclinical Profiles of Potent Pan-Genotypic Hepatitis E Virus Inhibitors,” at the Conference on Retroviruses and Opportunistic Infections, held last month in Denver.
Studies to evaluate AT-587’s effectiveness in animal models are ongoing, according to the company, and Atea expects to launch a Phase 1 clinical trial to test AT-587 in people in the coming months.
“We look forward to advancing AT-587 to a Phase 1 program mid-year,” Sommadossi said.
Hepatitis E is characterized by liver inflammation caused by HEV, which is typically transmitted via the fecal-oral route. Specifically, most people acquire the infection by drinking contaminated water or through food-borne transmission.
HEV is a major public health issue in parts of Asia and Africa, where certain strains — particularly genotypes 1 and 2 — are widespread. It’s also found in regions such as the U.S. and Europe, where different strains, usually genotypes 3 and 4, have been shown to circulate.
For most healthy people, HEV infection tends to be self-limiting, clearing on its own without long-term complications. However, the virus can be more dangerous in certain groups, including pregnant women and those with weakened immune systems. In these groups, the infection may not clear, increasing the risk of cirrhosis.
There is no approved treatment for hepatitis E
Treatment options for hepatitis E remain limited, with no medications to date that are specifically approved to target the virus. Doctors sometimes use off-label therapies, including sofosbuvir, ribavirin, or pegylated interferon-alpha, in selected cases.
Atea’s previous screening identified AT-587 and AT-2490 as potential anti-HEV medications. Both are prodrugs, meaning they are inactive compounds that are converted into an active drug within the body.
In the laboratory studies, AT-587 and AT-2490 were first shown to produce high levels of their active drug (AT-9068) in lab-grown human liver cells — the primary site of HEV infection.
The candidates’ effectiveness against HEV genotypes 1 and 3, including treatment-resistant strains, was then tested in a cellular model of human liver cells that is typically used to evaluate viral growth, or replication.
The results showed that both AT-587 and AT-2490 strongly blocked HEV replication, and were 30 to 150 times more potent against HEV than the antivirals sofosbuvir and ribavirin.
These results underscore the potential of AT-587 as a first-in-class direct acting antiviral for HEV.
No signs of toxicity were observed in human liver cells, heart muscle cells, or bone marrow cells, according to the researchers. The therapies also did not promote cancer-inducing mutations or heart rate problems.
“We are excited to share these preclinical results … showing the potent activity and promising … safety profiles of AT-2490 and AT-587, our HEV product candidate,” Sommadossi said. “These results underscore the potential of AT-587 as a first-in-class direct acting antiviral for HEV.”
Further experiments in the cellular model of human liver cells demonstrated that the antiviral activity of AT-587 and AT-2490 was not limited to the HEV. The two compounds were effective against a range of other viruses, including hepatitis C, dengue, yellow fever, and Zika.
Meanwhile, Atea’s experimental combination therapy of bemnifosbuvir and ruzasvir for chronic hepatitis C is in Phase 3 clinical testing. The global study, known as C-FORWARD (NCT07037277), is running in parallel with the North American Phase 3 C-BEYOND trial (NCT06868264).
