Dengue is a feverish, painful, and debilitating mosquito-borne infection caused by an RNA virus that may result in a severe, potentially fatal clinical syndrome called dengue hemorrhagic fever. There are four commonly recognized serotypes of dengue virus, numbered 1 through 4. An infection with one serotype does not protect against the others. A possible 5th dengue serotype was first described in 2006 but has not yet been found to be globally prevalent in World Health Organization analyses, which currently recognize only 4 major dengue serotypes.
It is not possible to accurately predict who is at risk for a severe or fatal form of dengue infection, though a high level of virus in the blood and previous dengue infection are risk factors for clinically severe dengue infections. Left untreated, severe dengue has a mortality rate of 12%-44%.
Dengue is estimated to account for 400 million infections a year globally, of which 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.
Although dengue rarely occurs in the U.S. and other areas outside the endemic regions, intercontinental jet transport, immigration, tourism, military operations and mosquito migration are increasing the direct effect of dengue on the global population. The mosquito vector that transmits dengue infection is becoming increasingly common in the southern U.S., and sporadic dengue infections are currently recognized in the American Gulf states. Some experts predict an increasing incidence of dengue infections in the American South, as global warming moves rising Gulf of Mexico waters inland.
The U.S. FDA, together with other governmental and non-governmental agencies, recognize dengue as a substantial and growing global public health burden. Dengue is designated as a disease that is eligible for FDA Priority Review Voucher Program.
Despite this increasing concern, there is no existing pharmaceutical treatment for dengue virus infection. Patients typically only receive supportive care through analgesics and judicious fluid therapy.
An oral, pan-serotypic antiviral requiring only a short treatment course would be a significant advance for the world’s many patients with dengue fever.
AT-752, a diastereomer of AT-527, is a novel purine nucleotide prodrug, designed to treat patients either newly infected or previously infected with the dengue virus. AT-752 has an excellent preclinical safety profile and has demonstrated potent in vitro activity against all dengue serotypes tested as well as efficacy in predictive animal models.
Building on these foundations, we plan to conduct clinical studies that will evaluate the daily administration of AT-752 over a short period of treatment, in order to negate the progression of infection and reduce the occurrence of life-threatening conditions associated with severe dengue.
As a dengue-specific therapeutic that can be administered orally for a short treatment course, AT-752 has the potential to be a critical contribution to dengue-related care and transmission.
We are focused on accelerating clinical development and seeking rapid market approval for our dengue antiviral therapeutic. With further progress, we also intend to explore addressing the traveler’s market by evaluating a preventative tablet.