Hepatitis E Drug AT-587 Enters First-in-Human Trial, Targeting Treatment Gap for Immunocompromised Patients

Hepatitis E is often regarded as an acute infection that resolves on its own, but in people who have undergone organ transplantation or hematopoietic stem cell transplantation, or who are receiving immunosuppressive treatment, the virus may persist and gradually lead to cirrhosis or even liver failure. There are currently no formally approved antiviral drugs for this group of chronically infected patients. Atea Pharmaceuticals has now advanced its oral drug candidate AT-587 into a first-in-human trial in an effort to fill this longstanding treatment gap.

EU clinical trial registry data show that the Phase 1 trial of AT-587 began in Belgium on July 13, 2026, and is currently recruiting. The study is expected to enroll 62 healthy adults at a single SGS Belgium trial site in Edegem, with Atea serving as the trial sponsor. This means the study’s first question is not whether the drug can clear the virus, but whether the human body can tolerate it safely and how the drug is absorbed, distributed, and eliminated after oral administration.

This randomized, double-blind, placebo-controlled study is divided into single ascending-dose and multiple ascending-dose parts and includes an assessment of the effect of food on drug exposure. Participants in the multiple-dose groups will take the drug once or twice daily for seven consecutive days. Whether subsequent doses are increased will be determined by the safety and pharmacokinetic data accumulated in the preceding stage.

AT-587 is a nucleotide analog being developed to inhibit hepatitis E virus replication. Atea said that, in study data presented at the 2026 annual meeting of the European Association for the Study of the Liver, the company observed that AT-587 had greater activity in cell-based experiments than ribavirin and sofosbuvir, which are currently used off-label, and reduced viral RNA in a gerbil model infected with genotype 3 virus. However, these findings primarily come from preclinical studies reported by the company and cannot yet be directly extrapolated to efficacy in humans.

Different hepatitis E virus genotypes vary in their modes of transmission and disease presentation. Genotypes 1 and 2 are mostly transmitted through contaminated water and often cause acute hepatitis. Genotype 3, which is more common in Europe and the United States, can be transmitted through food and can establish chronic infection in people with suppressed immune function. Atea has therefore focused the initial development of AT-587 on immunocompromised patients with chronic hepatitis E rather than on all patients with acute infection.

This trial is still only the starting point of development. Short-term dosing in healthy volunteers cannot demonstrate that AT-587 can reduce viral load in patients, improve liver function, or prevent cirrhosis. Nor is it sufficient to reveal the interactions and toxicities that may occur during long-term use in immunocompromised patients. Only if the safety and exposure findings support continued development, followed by clinical trials in infected patients, will AT-587 truly face the test of its therapeutic value.