Clinical pharmacology insights from recent cell and gene therapy approvals relevant to pediatrics

The United States Food and Drug Administration has approved 44 cell and gene therapies as of May 2025, including 14 for pediatric use (excluding cord blood). This signifies an advancement in the treatment of diseases and conditions that, as of yet, cannot be effectively managed with available small-molecule drugs and therapeutic proteins. This review explores the pharmacokinetic and first-in-human dosing considerations unique to cell and gene therapies. For in vivo gene therapies, development considerations include vector shedding and biodistribution. Traditional pharmacokinetic principles do not apply to ex vivo gene therapies, given the modification of cells outside the body before re-infusion. Cellular kinetics such as expansion and persistence are relevant in cell therapies like Chimeric Antigen Receptor T cells and Tumor Infiltrating Lymphocytes. A common trend of cell and gene therapy development is the reliance on preclinical models to inform safety, efficacy, and dose selection, with first-in-human dosing further guided by data from related therapies. Rare disease and pediatric drug development present additional challenges due to small patient populations, emphasizing the importance of preclinical evidence and safety considerations. The article outlines the key considerations for cell and gene therapies that are vital for expanding their use. IMPACT: This article provides a synthesis of pediatric rare disease clinical pharmacology considerations for recently approved cell and gene therapies, highlighting how advanced therapeutic products compare with traditional pharmacokinetic and pharmacodynamic frameworks used for small-molecule drugs. The development of advanced therapeutics depends on preclinical modeling, first-in-human dosing strategies, clinical trial design, and regulatory guidance for pediatric use, emphasizing the need for a practical primer on emerging advanced therapeutic products for researchers.