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Dengue is a global health emergency, with annually increasing case numbers that overwhelm healthcare systems, an ever-expanding range of the mosquito vector, and no antiviral or host-directed treatments proven to alter the course of disease. This article reports on a meeting of the Dengue Therapeutics Consortium, which included attendees from 19 countries with backgrounds in basic science, clinical research, drug development, industry, clinical trial methodology and policy. We summarise the current state of dengue therapeutics research and highlight the necessary steps to ensure that patients have equitable access to affordable and effective treatments. We review the antiviral pipeline, including novel and repurposed antiviral candidates, and we propose both human challenge and rate of viral clearance studies as methods to rapidly screen for antiviral activity prior to larger phase 3 clinical trials. We review ongoing phase 2 and phase 3 clinical trials to evaluate repurposed host-directed therapies for patients with moderate and severe disease, and we suggest considerations for future trial design, such as factorial randomisation and the use of a core outcome set to maximise efficiency and enable evidence synthesis by meta-analysis. We consider that multisectoral collaboration will be essential to achieve our aim of effective treatments for dengue. This will include drug development aligned to target product profiles, conduct of clinical trials with endpoints acceptable to both patients and regulators and sustained commitment from the pharmaceutical industry, non-profit initiatives and policymakers to ensure that effective treatments reach those who need them the most.
TL;DRThe antiviral pipeline, including novel and repurposed antiviral candidates, is reviewed, and both human challenge and rate of viral clearance studies are proposed as methods to rapidly screen for antiviral activity prior to larger phase 3 clinical trials. (Semantic Scholar)