Dengue is the most prevalent and important mosquito-borne virus in the world. Atea Pharmaceuticals presented positive data for their direct-acting dengue antiviral, AT-752.
Today, Atea Pharmaceuticals presented positive data from a phase 1 clinical trial for their dengue fever treatment, AT-752.
“Dengue is the most prevalent mosquito-borne virus,” said Atea Pharmaceuticals founder and CEO Jean-Pierre Sommadossi, PhD, “and despite its alarming increase over the last two decades, there are no direct-acting antiviral treatments available.”
Dengue causes an estimated 400 million infections each year. Among these, about 100 million people fall ill and half a million develop a potentially fatal dengue hemorrhagic fever. The World Health Organization (WHO) considers dengue “the most important mosquito-borne viral disease in the world.”
AT-752 is an orally administered, direct-acting antiviral, derived from Atea’s purine nucleotide prodrug platform. In its first human, dose-escalation study, it was found to have pan-serotype activity against dengue virus.
This study, shared today at the American Society of Tropical Medicine & Hygiene (ASTMH), included 65 healthy adults 18-65 years of age. The participants were randomized to either single ascending dose (SAD) or multiple ascending dose (MAD) cohorts, and then assigned to placebo or oral AT-752.
The participants receiving AT-752 quickly achieved plasma levels at or above the EC90 recorded in vitro. AT-752 was found to be safe and well tolerated, with no early discontinuations due to adverse events. Most adverse events that were recorded were mild, with no clinically relevant alterations in laboratory parameters. AT-752 had no pharmacokinetics sensitivity across the various ethnic populations enrolled in the study.
“Based on these data, we anticipate that AT-752 may have the potential to rapidly inhibit dengue virus replication across all serotypes (1-5),” Sommadossi said.
There are 4 common serotypes of dengue viruses, and a fifth that has been identified but not adequately characterized. Dengue serotypes are so antigenically different that infection with 1 serotype will generate antibodies against that serotype only. Later dengue infections with other serotypes significantly increases the risk of severe or fatal disease.
In light of the positive phase 1 results, Atea launched 2 subsequent, ongoing clinical studies of AT-752 for the treatment and prophylaxis of dengue. The first is a randomized, global, double-blind, placebo-controlled phase 2 trial of adults infected with dengue virus. It evaluates the safety, antiviral activity, and pharmacokinetics of multiple doses of AT-752 in areas where dengue is endemic. The second is a human challenge study being conducted in the US.
Dengue is endemic in over 100 countries, including equatorial regions like Puerto Rico, Southeast Asia, Latin America, and the Pacific Islands. The virus occasionally spreads to the continental US, a spread exacerbated because the types of mosquitoes that spread dengue are common in many parts of the US.
This study, “Safety, tolerability, and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus: results from a Phase 1, first-in-human, dose-escalation study,” was presented at the American Society of Tropical Medicine & Hygiene (ASTMH) 2022 Annual Meeting in Seattle, Washington.