By NewsDesk @bactiman63
Clinical-stage biopharmaceutical company, Atea Pharmaceuticals, Inc., today presented a poster highlighting favorable AT-752 Phase 1 clinical data for the treatment of dengue fever at the American Society of Tropical Medicine & Hygiene (ASTMH) 2022 Annual Meeting in Seattle, Washington.
The poster #1358, titled “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 by Xiao-Jian Zhou, PhD, Executive Vice President of Early Stage Development at Atea Pharmaceuticals.
“Dengue is the most prevalent mosquito-borne virus and despite its alarming increase over the last two decades, there are no direct-acting antiviral treatments available,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and Founder of Atea Pharmaceuticals. “These data demonstrate that AT-752 was well tolerated up to the highest dose tested and rapidly achieved plasma levels above the in vitro EC90. Based on these data, we anticipate that AT-752 may have the potential to rapidly inhibit dengue virus replication across all serotypes (1-5). In addition, AT-752 exhibited no pharmacokinetic sensitivity across varying ethnic populations participating in the trial.”
“Importantly, these results support our advancement of two proof-of-concept studies to demonstrate AT-752’s safety and efficacy for the treatment and potential prophylaxis of dengue,” continued Dr. Sommadossi.
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Atea is currently conducting two AT-752 clinical studies. The first study is a global, randomized, double-blind, placebo-controlled Phase 2 trial in adult patients with dengue virus infection. The study is designed to evaluate the antiviral activity, safety and pharmacokinetics (PK) of multiple doses of AT-752 in areas where dengue is endemic. The second study is a human challenge study that is being conducted in the United States. The challenge study is designed to evaluate healthy subjects who are challenged with a Dengue Virus-1 Live Attenuated Virus strain after receiving AT-752 or placebo.
AT-752, a novel, orally administered direct-acting antiviral derived from Atea’s purine nucleotide prodrug platform was designed for the treatment and prophylaxis of dengue. It works by impairing the dengue viral polymerase, which then inhibits replication of the virus. In preclinical studies, AT-752 showed potent in vitro activity against all dengue serotypes, as well as potent in vivo antiviral activity in a small animal model.
The U.S. 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 the Phase 1 study, 65 healthy subjects aged 18–65 years old were sequentially enrolled into single ascending dose (SAD) and multiple ascending dose (MAD) cohorts and randomized to receive oral AT-752 or placebo. AT-752 was administered as a single oral dose up to 1500 mg, or as multiple oral doses up to 750 mg three times a day. In this study, AT-752 rapidly achieved plasma levels exceeding the in vitro EC90. AT-752 was generally safe and well tolerated and no premature discontinuations due to adverse events or serious adverse events were reported. Most adverse events were mild and there were no clinically relevant changes in laboratory parameters. AT-752 exhibited no PK sensitivity across varying ethnic populations participating in the trial and no food effect was seen.
The overall safety and PK results obtained in this Phase 1 study supported the initiation of two clinical studies of AT-752 for the treatment and prophylaxis of dengue infection.
About Dengue Fever
It is estimated that dengue accounts for up to 400 million infections a year globally, of which 100 million people get sick from the infection and 500,000 cases develop into life-threatening dengue hemorrhagic fever. Dengue infection is currently endemic in equatorial regions of the world, including Puerto Rico, Southeast Asia, Latin America and the Pacific Islands. Dengue occurs occasionally in the continental U.S. and other areas outside the endemic regions. However, because the types of mosquitoes that spread dengue are common in many parts of the continental U.S., local spread of the disease is possible. In addition, intercontinental jet transport, immigration, tourism, military operations and mosquito migration are increasing the direct effect of dengue on the global population.
Four serotypes of dengue viruses (DENV1–4) are common and a fifth serotype has been isolated but is yet to be fully characterized. As dengue serotypes are sufficiently different antigenically, infection with one serotype will confer lifelong immune protection against that serotype only, with only temporary, partial cross-immunity to other serotypes following recovery. A person can therefore potentially be infected with each dengue serotype in their lifetime. Subsequent infections with other serotypes increase the risk of developing severe disease due to antibody-dependent enhancement (ADE).
The World Health Organization has called dengue the most important mosquito-borne viral disease in the world. The FDA, together with other governmental and non-governmental agencies, recognize dengue as a substantial and growing global public health burden. Dengue is defined as a tropical disease under the U.S. 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 voucher that may be used for a subsequent NDA or biologics license application.
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