A comprehensive analysis of cell and gene therapy (CGT) submissions has uncovered significant disparities in clinical trial data presented to U.S. and European regulatory authorities, potentially complicating the approval pathway for these innovative treatments.
Research published in JAMA Internal Medicine examined 15 CGT products submitted to both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) through October 2023. The findings revealed that only 20% of trials submitted to both agencies contained matching evidence, raising concerns about regulatory consistency.
Data Discrepancy Analysis
The study identified substantial variations in trial reporting between the two regulatory bodies. Of 20 trials reported to both agencies, 13 demonstrated different sample sizes, with eight showing variations exceeding 10%. The EMA received larger sample sizes in six of these cases.
Further analysis revealed that 13 out of 19 trials with comparable endpoints reported different efficacy outcomes between FDA and EMA applications. Six of these trials showed outcome differences greater than 10%.
A notable example involves Hemgenix (etranacogene dezaparvovec), a gene therapy for hemophilia B, where the reported annual bleeding rate was 22% higher in FDA submissions compared to EMA data, despite identical trial sample sizes.
Therapeutic Focus and Impact
Most applications centered on gene therapies targeting rare diseases, with oncology emerging as the predominant therapeutic area. The researchers, led by Dr. Magdi Elsallab of Harvard Medical School, emphasized that while some outcome variations may stem from different regulatory requirements or submission timing, the extent of these differences warrants closer examination.
Regulatory Harmonization Initiatives
In response to these challenges, regulatory bodies have launched several harmonization efforts:
- The Collaboration on Gene Therapies Global Pilot, announced by FDA's CBER Director Dr. Peter Marks in January 2024, aims to coordinate evidence requirements across global agencies
- FDA's START pilot program seeks input on challenges in developing CGTs for rare diseases with limited patient populations
- As of December 2024, the FDA has approved 43 cell and gene therapies, including various stem cell treatments
Future Implications
The research team suggests that implementing uniform evidence standards and reporting requirements could accelerate patient access while maintaining rigorous safety and efficacy evaluations. However, they acknowledge that limited information about sponsor-agency interactions may have influenced the observed differences.
The findings underscore the critical need for standardized approaches in CGT development, as harmonized regulatory processes could significantly impact the efficiency of bringing these innovative therapies to patients.
