WHO defines clinical, safety and access targets for non-severe and severe dengue treatments as six drug candidates advance toward late-stage development.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
The World Health Organization (WHO) has published target product profiles (TPPs) defining the clinical, safety, formulation, and access standards for treatments for non-severe and severe dengue, providing developers with a structured framework for advancing candidates into pivotal trials.
Dengue Lacks a Specific Treatment
Dengue is expanding with climate and demographic change. The disease is endemic in more than 100 countries, placing nearly half of the global population in tropical and subtropical regions at risk.
Despite this burden, no licensed dengue-specific treatment exists. Supportive care and volume replacement remain the clinical standard, while progression from acute febrile illness to vascular leak, bleeding, shock, organ failure, and death remains a major risk. The TPPs define the clinical and product characteristics needed for future treatments for both non-severe and severe disease.
Six Dengue Drug Candidates Emerge in Late-Stage Development
WHO’s pipeline analysis identified 21 relevant clinical trial records involving 15 medicinal products. Six candidates with positive dengue-related in-vivo efficacy data were considered sufficiently advanced for further development: five novel agents and one repurposed drug.
The group comprises:
- Antivirals: mosnodenvir, fenretinide, EYU688, VIS513, and AV-133
- Host-directed therapy: resomelagon
The candidates span several mechanisms of action. Mosnodenvir and EYU688 inhibit dengue NS4B, fenretinide targets NS5, and the monoclonal antibodies VIS513 and AV-1 target envelope protein domains III and II, respectively. Resomelagon acts through melanocortin receptors 1 and 3.
Three antiviral candidates, mosnodenvir, fenretinide, and VIS513, completed industry-sponsored Phase 2 studies with positive efficacy findings involving reductions in viraemia and symptom duration. EYU688 and AV-133 remained in Phase 2 development, while resomelagon was starting recruitment in an academic-led Phase 2 study.
VIS513 is currently the only candidate with confirmed plans for Phase 3 natural-infection testing, with enrollment including adults and children aged 5 years and older. Mosnodenvir’s Phase 2 field studies were terminated following sponsor portfolio reprioritisation.
WHO Defines Clinically Meaningful Phase 3 Endpoints
- Non-severe dengue: WHO recommends direct clinical outcomes rather than viral markers as primary efficacy measures. The minimum primary endpoint is a reduction in time to resolution of acute symptoms, with a minimally important difference of one day. Under the optimal profile, reduction in progression to severe dengue, measured by dengue-related hospitalization needs within 28 days, becomes the primary endpoint.
- Severe dengue: The central endpoint is a reduction in organ failure requiring organ support, measured by the need for non-invasive or mechanical ventilation, vasopressors or inotropes, renal replacement therapy, plasma exchange, or albumin dialysis. Major bleeding is a key secondary endpoint, while mortality within 28 days is included under the optimal criteria.
Access and Safety Are Part of the Product Target
WHO recommends broad Phase 3 inclusion, encompassing children, older adults, and people with common comorbidities such as diabetes and obesity. Pregnancy and lactation are included in the optimal criteria, with reproductive-toxicity studies expected before Phase 3 to support dedicated pharmacokinetic and safety studies.
- Non-severe disease: The optimal profile calls for an oral therapy requiring no more than three days of treatment and once-daily or less frequent dosing. The minimum profile allows treatment for up to seven days and dosing two to three times daily.
- Severe disease: Intravenous treatment remains preferred because vascular leak can compromise enteral absorption.
Both profiles emphasise stability across tropical climates, minimal monitoring requirements, and pricing compatible with broad access in dengue-endemic countries.
A Framework for the Next Dengue Drug Wave
The TPPs give developers and regulators a common benchmark for Phase 3 evidence while linking therapeutic development to rapid pathogen-confirming diagnostics. WHO also recommends combination therapies to reduce the risk of antiviral resistance and calls for access strategies that support fair pricing and rapid deployment in endemic countries.
With VIS513 entering Phase 3 and WHO establishing clearer requirements for pivotal dengue trials, the field is entering a more decisive stage of therapeutic development.
Reference
Chan X, Durbin A, Malavige G et al, Accelerating the clinical development of treatments for dengue: WHO dengue therapeutics landscape analysis and target product profiles, The Lancet Microbe, 2026; 0, https://doi.org/10.1016/j.lanmic.2026.101451
Target product profiles for treatments for dengue, World Health Organization, 08 May 2026
WHO issues first ever guidance to advance child-focused dengue treatments, World Health Organization, 15 June 2026
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.