To accelerate innovation in therapeutics to prevent the progression of dengue to severe disease
current phase of drug development
updated 4 Mar 2025
Dengue fever, a climate-sensitive disease, is an important cause of morbidity and mortality in endemic countries, but drugs to prevent and treat the disease are lacking. The incidence of dengue fever has increased dramatically over recent decades, and treatments that prevent dengue infection from progressing to severe disease – known as dengue haemorrhagic fever – are urgently needed. Together with our partners, DNDi is prioritizing drug development, with a focus on pregnant women, young children, and people with comorbidities who are more likely to suffer greater morbidity and mortality.
DNDi’s short-term strategy is to work with partners to repurpose existing direct-acting antivirals (DAAs) and host-directed therapies capable of inhibiting the inflammatory response characteristic of severe disease. Over the medium-term, DNDi is working with partners to develop novel antivirals, with four candidates showing in vivo efficacy in preliminary testing.
Dengue Alliance: a global partnership to develop affordable and accessible treatments for dengue
This project is led by the Dengue Alliance, a global partnership of institutions from dengue-endemic countries launched in 2022 to develop affordable and accessible treatments for dengue.
Project updates
2024
Dengue Alliance partners continued studying potential candidates for entry into clinical studies with three host-directed therapy (HDT) targets undergoing further in vivo and in vitro assays to validate their effects and provide the basis for dose selection. In addition, a number of repurposed antiviral treatments were selected for potential progression into first-in-human studies, pending dose selection and safety evaluations.
2023
Dengue Alliance partners continued in vitro evaluation of existing direct-acting antiviral (DAA) compounds, with prioritized compounds advancing in in vivo testing in India and Brazil. Partners also initiated pre-clinical evaluation of existing host-directed therapies (HDTs), including a compound identified by BenevolentAI’s artificial intelligence-driven drug discovery platform that has been found to inhibit increases in endothelial cell permeability in vitro. With the nomination of DAA and HDT candidates expected in 2024, DNDi and partners also advanced preparations for clinical studies, including finalization of study endpoints, selection of study population, and discussions with potential industry partners on integrating novel DAAs and HDTs alongside repurposing candidates.
2022
Three existing direct-acting antiviral (DAA) compounds – GS-441525, niclosamide, and nelfinavir – have been evaluated for their ability to inhibit the dengue virus. These compounds have advanced to in vivo efficacy studies after initial pharmacokinetic evaluations. Discussions are ongoing to determine the best host-directed therapies and methods for evaluating them, considering the diverse range of modes of action. A clinical synopsis for Phase II studies is under development and will be finalized by the third quarter of 2023.
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