Enhancing Drug Development for Paediatric Pulmonary Hypertension—An Integrative Perspective

As with adult pulmonary hypertension (PH), high morbidity and mortality persist with diverse types of paediatric PH. Despite major advances in pharmacologic therapies based on extensive studies in adult PH, few drugs have been comprehensively studied in neonates, infants, and children, leaving current paediatric PH care largely dependent on small observational studies and extrapolation of evidence from adult clinical trials. Challenges in developing successful clinical trials in children include the need to define distinct disease phenotypes with well-characterised natural history and outcomes, the lack of established age- and disease-specific study endpoints, small and heterogeneous paediatric populations, and the common off-label use of PH-targeted drug therapies without regulatory approval. From a regulatory perspective, sufficient studies of safety, pharmacokinetics, and pharmacodynamics in neonates and young children are often lacking, and the potential role for bridging biomarkers has been underexplored. Additional opportunities include developing innovative trial designs, employing real-world data from existing registries, and fostering collaborations among sponsors, regulatory authorities, physicians, patients, and their families. By reducing reliance on off-label drug use and leveraging paediatric PH registry data, this approach offers a path toward more effective and evidence-based treatment protocols for paediatric patients. This review provides an overview of integrated international perspectives from an interprofessional platform that includes academia, the pharmaceutical industry, and regulatory agencies surrounding the future design of clinical trials for paediatric PH. Ongoing evaluation and adaptation of these strategies will be essential for ensuring that paediatric PH patients receive the highest standard of care.