Gene Therapy Drug Development for First-In-Human Study of Pediatric Diseases: Facilitating Change to Current Paradigms

Abstract

Drug development in pediatrics is mandated under US and European Union legislation, and delays in pediatric studies can impact the appropriate labeling and use of therapeutics for children. Developing medical products for pediatrics is challenging, as there are several critical issues and factors to consider when initiating a pediatric drug development program. The International Conference Harmonisation guideline E11(R1) and criteria under 21 CFR part 50 subpart D define pediatric regulatory standards for drug developers and ensure the safety of pediatric participants in clinical studies. Adequate adult data are typically required before finalizing pediatric study designs and initiating pediatric studies by virtue of the Pediatric Research Equity Act. It is evolving that the Food and Drug Administration (FDA) is including adolescents in Phase 3 trials. In pediatrics, the lack of coordinated use of extrapolation for safety and efficacy amongst global regulatory agencies impacts the timelines and development of clinical trial designs. First-in-human pediatric trials may be justified if the aspects of 21 CFR 50, subpart D specifically 21 CFR 50.52 are addressed. For example, first-in-human pediatric gene therapy trials have been allowed in spinal muscular atrophy (SMA) using a benefit-risk assessment to justify the conduct of first-in-human trials in children. The statutory requirement to study children in clinical trials is influenced by the nature of the disease that is currently under study and needs to be personalized. These issues are addressed in this perspective on gene therapy treatment in children.