Presentation (CTI)

OBJECTIVES: The One Big Beautiful Bill Act, signed 7/4/25, expanded the Inflation Reduction Act’s Orphan Drug Exclusion (ODE) making orphan drugs ineligible for Medicare negotiation, from drugs treating one and only one rare disease to those treating “one or more rare diseases.” This study describes the characteristics of drugs receiving a second orphan designation following the ODE expansion that reduced the disincentive to seeking such designations.
METHODS: Orphan designations granted from 7/5/2025-1/5/2026 were obtained from the Food and Drug Administration (FDA)’s orphan drug database. Designations representing a second active designation for a given drug and manufacturer were identified by manual review (two PharmDs) using the FDA database and PharmaProjects. Drugs were excluded if FDA-approved for at least one nonorphan indication before 7/5/25. Therapeutic area, drug modality, and dates of European Union orphan designations were obtained from PharmaProjects. US disease prevalence estimates were recorded from targeted review of the SEER website, FDA briefing documents, and the Genetic and Rare Diseases Information Center. Drug and designation characteristics were summarized using descriptive statistics.
RESULTS: In the 6 months following ODE expansion, manufacturers of 27 orphan drugs received a second active designation. Most drugs (n = 15, 55.6%) were designated in rare cancers. Drugs receiving a second active designation were more often biologics (n = 13, 48.1%) than small molecule drugs (n = 10, 37.0%). Three drugs (11.1%) were cell or gene therapies. At least 12 (44.4%) of designations were in conditions affecting fewer than 50,000 Americans. For the subset of designations that could be identified in PharmaProjects, nine in ten (n =23/25, 92.0%) were obtained in the US prior to the European Union.
CONCLUSIONS: Second orphan drug designations following ODE expansion were concentrated in oncology and typically obtained earlier in the US than the EU. Future research will explore additional characteristics and comparative findings.