Presentation (CTI)

OBJECTIVES: Cell and gene therapies (CGTs) are changing how chronic and rare diseases are treated. As regulatory systems continue to evolve globally, it is important to understand the similarities and differences between decisions made by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This analysis reviewed the FDA approval status of orphan CGTs and compared it with EMA decisions, focusing on approval timelines, withdrawals, refusals, and the reasons behind them.
METHODS: The FDA website was searched for all authorized orphan CGTS. The EMA website was searched for the corresponding approval in Europe with approval date, orphan designation status, and indication noted.
RESULTS: As of 25^th November 2025, the FDA has approved 46 CGTS, 31 with orphan status. Of these, the EMA has approved 15 (33%), of which 12 were approved with orphan designation. Three EMA-approved CGTs later had their marketing authorizations voluntarily withdrawn by the manufacturer, all citing commercial concerns. Additionally, two products had their EMA marketing authorization application withdrawn or refused due to insufficient efficacy evidence. Analysis of authorization dates showed that 8 orphan CGTs were first approved by the FDA. EMA authorization followed an average of 294 days later. Conversely, four orphan medicines received initial approval from the EMA, with subsequent FDA approval occurring after an average of 312 days. These findings will be compared with our findings from 2024 to identify any trends in decision-making.
CONCLUSIONS: Regulatory outcomes for orphan CGTs differ markedly between the FDA and EMA. These differences reflect variations in evidence requirements and assessment frameworks. EMA withdrawals driven by commercial considerations and refusals linked to inadequate efficacy data further illustrate the challenges in achieving dual-market access. While some therapies do progress to approval through both agencies, many do not, highlighting the need for earlier and more coordinated evidence generation strategies.