Dengue fever treatment: Favorable Phase 1 clinical data presented at ASTMH meeting
by NewsDesk Lord save her
Clinical Phase Biological Pharmaceutical Company, Atea Pharmaceuticals, Inc.today presented a poster highlighting favorable clinical data for Phase I AT-752 for the treatment of dengue fever at the American Society for Tropical Medicine and Health (ASTMH) 2022 Annual Meeting in Seattle, Washington.
Poster No. 1358, titled “Safety, Tolerability, and Pharmacokinetics of AT-752, a New Nucleotide Prodrug with Mass Serotyped Activity Against Dengue Virus: Results from a Phase I, First-Dose-escalation Study in Human,” was submitted by Xiao-Jian Zhou. , Ph.D., executive vice president of early stage development at Atea Pharmaceuticals.
“Dengue is the most prevalent mosquito-borne virus, and despite an alarming increase over the past two decades, no direct antiviral treatments are available,” said Jean-Pierre Somadosi, PhD, CEO and founder of Atea Pharmaceuticals. These data show that AT-752 was well tolerated up to the highest dose tested and achieved plasma levels above in the laboratory EC90. Based on these data, we speculate that AT-752 may have the ability to rapidly inhibit dengue virus replication across all serotypes (1–5). In addition, AT-752 did not show any pharmacokinetic sensitivity across the different ethnic groups participating in the experiment.”
“Importantly, these results support our progress in two proof-of-concept studies to demonstrate the safety and efficacy of AT-752 in the treatment and potential prevention of dengue,” Dr. Somadossi continued.
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Atea is currently conducting two clinical studies of the AT-752. The first study is a global, phase 2, randomized, double-blind, placebo-controlled trial in adult patients with dengue virus infection. The study was designed to evaluate the antiviral activity, safety and pharmacokinetics (PK) of multiple doses of AT-752 in dengue-endemic areas. The second study is the Human Challenge Study that is being conducted in the United States. The challenge study was designed to evaluate healthy subjects challenged with the Virus-1 Live Attenened Virus strain of dengue after receiving AT-752 or a placebo.
AT-752, a novel, direct-acting orally administered antiviral derived from Atea’s purine nucleotide drug platform is designed for the treatment and prevention of dengue fever. It works by impairing dengue viral polymerase, which then prevents virus replication. In preclinical studies, AT-752 has been shown to be effective in the laboratory Activity against all dengue serotypes, as well as potent in vivo Antiviral activity in a small animal model.
The US Food and Drug Administration (FDA) has granted fast-track designation to AT-752 for the treatment of dengue virus infection.
AT-752 Phase 1 Study Results
In a phase I study, 65 healthy subjects aged 18–65 years were sequentially enrolled in a single ascending dose (SAD) and multiple ascending dose (MAD) and randomized to receive AT-752 oral or placebo. AT-752 has been administered as a single oral dose of up to 1500 mg, or as multiple oral doses of up to 750 mg three times a day. In this study, AT-752 rapidly achieved plasma levels that exceeded in the laboratory EC90. AT-752 was generally safe and well tolerated and no premature discontinuation of adverse events or serious adverse events was reported. Most adverse events were mild and there were no clinically relevant changes in laboratory parameters. AT-752 showed no sensitivity to PK across the varying ethnic groups participating in the experiment and no dietary effect was observed.
The general safety and PK results obtained in this phase I study supported the initiation of two clinical studies of AT-752 for the treatment and prevention of dengue infection.
It is estimated that dengue causes up to 400 million infections annually globally, of which 100 million people fall ill from the infection and 500,000 cases develop into the life-threatening dengue hemorrhagic fever. Dengue infection is currently endemic in tropical regions of the world, including Puerto Rico, Southeast Asia, Latin America, and the Pacific Islands. Dengue fever occasionally occurs in the continental United States and other areas outside endemic areas. However, because the types of mosquitoes that spread dengue are common in many parts of the continental United States, it is possible for the disease to spread locally. In addition, transcontinental transport, migration, tourism, military operations, and mosquito migration increase the direct impact of dengue fever on the global population.
Four serotypes of dengue virus (DENV1–4) are common and serotype V has been isolated but not yet fully characterized. Because dengue serotypes differ sufficiently in terms of antigens, infection with one serotype will confer lifelong immune protection against that serotype only, with temporary and partial cross-immunity to other serotypes after recovery. Therefore, a person is likely to contract every dengue serotype in their lifetime. Subsequent infection with other serotypes increases the risk of severe disease due to antibody-dependent enhancement (ADE).
The World Health Organization has described dengue fever as the world’s most important mosquito-borne viral disease. The U.S. Food and Drug Administration, along with other governmental and nongovernmental agencies, recognize dengue fever as a significant and growing burden on global public health. Dengue is defined as a tropical disease under the United States Food, Drug, and Cosmetic Act, and therefore, FDA approval of AT-752 for the treatment or prevention of dengue may result in the award of a Tropical Disease Priority Review Coupon which can be used to request Subsequent license to NDA or Biology.
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