April 9, 2026 —
Officials from the U.S. Food and Drug Administration (FDA) highlighted significant progress in regulatory science that has supported the rapid growth of the cell and gene therapy sector, while experts at a recent meeting emphasized that challenges remain—particularly when it comes to enrolling pediatric patients in clinical trials.
The discussion took place during a joint meeting hosted by the FDA and the Alliance for Regenerative Medicine (ARM) focused on the development of advanced therapies for children with rare and serious diseases.
During the meeting, Najat Bouchkouj, Associate Director of Pediatrics at the Office of Therapeutic Products (OTP) within the FDA’s Center for Biologics Evaluation and Research (CBER), highlighted the substantial expansion of the field in recent years. According to the agency, 33 cell and gene therapies have now been approved in the United States, including 28 gene therapies and five cell therapies, with more than half approved for pediatric use.
Despite this progress, regulators and industry leaders acknowledged that developing cell and gene therapies—especially for rare pediatric diseases—remains complex. Vijay Kumar, Acting Director of the Office of Therapeutic Products, noted that developers often face challenges including limited patient populations, incomplete natural history data, and difficulty defining appropriate clinical endpoints and biomarkers.
Additional barriers include geographically dispersed patient populations, missing or incomplete clinical data, and misalignment between clinical development timelines and chemistry, manufacturing, and controls (CMC) requirements. These challenges are particularly significant for advanced therapies, which frequently involve complex manufacturing processes and highly individualized treatment approaches.
Kumar noted that emerging technologies are helping bridge these gaps in evidence generation. The FDA has increasingly embraced real-world data and real-world evidence derived from electronic health records and disease registries, as well as digital health technologies such as wearable devices that can continuously monitor patient outcomes. In addition, artificial intelligence and advanced data analytics are enabling sponsors to better analyze complex datasets and identify treatment effects in small patient populations.
Regulatory initiatives are also evolving to support innovation in rare disease drug development. Kumar highlighted several recent programs, including the Rare Disease Endpoint Advancement (RDEA) pilot program, which explores novel efficacy endpoints for rare diseases, as well as the agency’s plausible mechanism designation and the increasing use of Bayesian statistical approaches that integrate prior scientific knowledge with new clinical data.
“We are building a modern regulatory framework that is both rigorous and responsive,” Kumar said during the meeting.
While regulatory flexibility has expanded, experts at the meeting stressed that historical caution still affects the inclusion of children in early-stage clinical trials. Crystal Mackall, founding director of the Stanford Center for Cancer Cell Therapy, explained that long-standing concerns about safety in pediatric trials continue to influence both regulators and industry sponsors.
Historically, Phase 1 clinical trials were rarely conducted in children because early trials often produced poor outcomes and significant toxicity. Mackall argued that these historical perceptions may no longer reflect current scientific advances in precision cell and gene therapies.
She cited ongoing development of a B7-H3–targeted CAR-T therapy for pediatric solid tumors at Stanford. Although earlier versions of the therapy showed some toxicities, the treatment has since been modified to improve safety. Despite these improvements, Mackall noted that there remains hesitation among both regulators and sponsors to begin trials directly in pediatric populations.
According to Mackall, the FDA typically prefers that adult patients be enrolled first, sometimes requiring a minimum number of adult participants before pediatric studies can begin. She argued that this approach may not always be appropriate when a therapy is specifically designed to treat childhood diseases.
FDA officials acknowledged the importance of continued dialogue. Lynne Yao, Director of the Center for Drug Evaluation and Research (CDER) Pediatric and Maternal Health Center, emphasized that researchers and developers must be willing to challenge traditional assumptions in order to bring innovative therapies to children.
“You have to be brave to be in this space,” Yao said, encouraging developers, regulators, and academic investigators to work together to expand access to novel therapies for pediatric patients.
The discussion also addressed the minimum evidence requirements needed before enrolling children in clinical trials. Mackall suggested that several key criteria should be met, including confirmation that the therapy targets a biologically relevant disease mechanism, evidence of a plausible therapeutic mechanism, and sufficient safety data from preclinical studies.
However, she noted that existing preclinical models often fall short in predicting safety and efficacy, making regulatory decision-making particularly challenging.
Overall, participants agreed that continued collaboration among regulators, researchers, and industry will be essential to advance the development of cell and gene therapies for pediatric diseases, while ensuring appropriate safeguards for vulnerable patient populations.
