Paediatric Drug Optimization for Sickle Cell Disease: priorities for research and development in children

Sickle cell disease remains a major cause of childhood morbidity and mortality, particularly in sub-Saharan Africa. In September, 2025, WHO convened the Paediatric Drug Optimization for Sickle Cell Disease process to review approved therapies, pipeline candidates, and potentially curative approaches, and define priorities for children and adolescents. Hydroxyurea (hydroxycarbamide) was confirmed as the leading near-term priority, with age-appropriate soluble or dispersible formulations identified as essential to improve equitable paediatric access; preferred and minimum characteristics were defined through a formal target product profile. Among investigational agents, pyruvate kinase activators and decitabine plus tetrahydrouridine (NDec) emerged as promising candidates for paediatric investigation on the basis of emerging efficacy data and programmatic potential. Intersecting research priorities included identifying appropriate clinical trial endpoints, strengthening early and inclusive paediatric investigation, and proactively ensuring that the promise of potential cure through gene therapy does not delay investment in scalable disease-modifying treatments.