Orphan Designation for Drugs Approved in the United States and European Union: A Comparative Analysis

Rare disease drugs represent a significant portion of new drug approvals, but the United States and European Union (EU) have differing approaches to Orphan Drug designations, impacting application fees and market exclusivity. This cross-sectional study analyzed the first rare disease drug approvals in the United States and EU from 2011 to 2020 using data from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) databases, describing similarities and differences in how both regions grant Orphan Drug designations. Out of 344 rare disease drug approvals, 336 (97.7%) were licensed by the FDA with Orphan Drug designations, 139 (40.4%) by the EMA with Orphan Drug designations; 131 (38.1%) were licensed with Orphan Drug designations by both the FDA and EMA, while 103 (29.9%) were approved in the EU without this designation. Additionally, 110 (32.0%) had approval from one agency only, with 102 (29.7%) by the FDA and 8 (2.3%) by the EMA. Both agencies were most consistent in granting Orphan Drug designations for advanced therapies (75.0%) and genetic diseases (55.4%). EMA approvals were lacking for tropical diseases (12.7%), while EU designations were often absent for diseases not considered distinct entities, such as subsets of cancers or pediatric indications of prevalent diseases. These findings reflect the differing regulatory frameworks and practices between the United States and the EU. Policymakers seeking to improve rare disease drug approval could prioritize incentives for the development of treatments for truly rare diseases as opposed to subsets of more common conditions for which incentives have already been established or create pathways that tackle scientific and societal challenges.