Massachusetts-based Atea Pharmaceuticals (Nasdaq: AVIR) has dosed the first participants in a Phase I clinical trial of AT-587, an oral nucleotide analog prodrug for hepatitis E virus (HEV), advancing what could become the first dedicated antiviral therapy for a disease with no approved treatments.
The randomized, double-blind, placebo-controlled Phase I study is evaluating single- and multiple-ascending doses of AT-587 in healthy volunteers, with primary endpoints of safety, tolerability, and pharmacokinetics. A food-effect assessment is also included. The study represents the first clinical evaluation of AT-587 after the company selected the compound as its lead HEV candidate in 2025.
Chronic HEV infection primarily affects immunocompromised patients, particularly solid organ transplant recipients and other individuals receiving long-term immunosuppressive therapy. Although ribavirin is widely used off-label, its efficacy is variable and treatment can be limited by toxicity and the emergence of resistance mutations, leaving a significant unmet medical need.
AT-587 is an oral nucleotide analog prodrug designed to inhibit the viral RNA-dependent RNA polymerase. Preclinical data presented at the EASL Congress 2026 showed activity against HEV variants associated with resistance to both ribavirin and sofosbuvir, while demonstrating substantially greater antiviral potency than either comparator in laboratory models. Previous attempts to repurpose Gilead Sciences' hepatitis C drug sofosbuvir for chronic HEV have produced disappointing clinical results, reinforcing interest in therapies specifically optimized for the virus.