Characterizing early oncology Orphan Drug Designation activity following expansion of the Orphan Drugs Exclusion.

Abstract

e23050 Background: The Inflation Reduction Act (IRA) Medicare Drug Price Negotiation Program’s (DPNP) Orphan Drug Exclusion (ODE) was limited to orphan drugs designated only for “a single rare disease or condition” — generating concerns about the ODE’s impact on incentives for ongoing clinical development for rare disease treatments. The One Big Beautiful Bill Act, signed 7/4/25, expanded the ODE from drugs treating only a single rare disease to those treating “one or more rare diseases.” This expansion may preserve incentives for seeking additional orphan designations, which could particularly benefit rare cancer drug development. This study describes the characteristics of oncology drugs receiving a second orphan designation - and disease characteristics of those designations - following the ODE expansion. Methods: We obtained orphan designations granted from 7/5/2025-1/5/2026 from the orphan drug database maintained by the Food and Drug Administration (FDA). Oncology 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. Drug modalities and dates of European Union (EU) orphan designations were obtained from PharmaProjects. US disease prevalence estimates were recorded from a targeted review of the SEER and cancer foundation websites as well as peer-reviewed literature. Drug and designation characteristics were summarized using descriptive statistics. Results: In the 6 months following ODE expansion, manufacturers of 15 orphan drugs received a second active designation. Drugs receiving a second active designation were more often biologics (n = 8, 53.3%) than small molecule drugs (n = 5, 33.3%). The two remaining drugs were a cell therapy (6.7%) and a cancer vaccine (6.7%). A total of 11 unique designations were received across 10 unique cancers, primarily (n = 8) solid tumor cancers. Over 1 million (estimated at approximately 1.15M) Americans are currently living with one of the 10 orphan-designated cancers. For the subset of designations that could be identified in PharmaProjects, all 14 (100%) were obtained in the US prior to the EU. Conclusions: Second orphan drug designations following ODE expansion were obtained by manufacturers of 15 orphan drugs across 10 unique cancers currently affecting approximately one million Americans. These second orphan designations were obtained earlier in the US than in the EU. These descriptive findings provide an early view of second orphan drug designations following the ODE expansion, which may preserve incentives for research into multiple rare diseases. Future research will explore additional characteristics and comparative findings.