CLINICAL DEVELOPMENT LANDSCAPE AND CHARACTERISTICS OF RARE DISEASES IN THE U.S.
Author(s)
Hanke Zheng, MS, PhD1, Tyler D. Wagner, PharmD, PhD2, Jon Campbell, PhD3;
1National Pharmaceutical Council, Research Manager, Washington, DC, USA, 2National Pharmaceutical Council, Richmond, VA, USA, 3National Pharmaceutical Council, Washington, DC, USA
1National Pharmaceutical Council, Research Manager, Washington, DC, USA, 2National Pharmaceutical Council, Richmond, VA, USA, 3National Pharmaceutical Council, Washington, DC, USA
OBJECTIVES: To describe the recent clinical development landscape and key characteristics of rare diseases in the U.S.
METHODS: Using the U.S. Food and Drug Administration (FDA)’s orphan drug designation database, we identified orphan designations granted for the treatment or prevention of rare diseases in 2025 and restricted the sample to non-FDA-approved treatments. We used two AI-assisted tools to classify whether the designated conditions had existing FDA-approved therapies, and two researchers independently validated the classifications. Focusing on rare diseases without existing approved treatments, we characterized the orphan-designated treatments and therapeutic areas.
RESULTS: In 2025, N=389 orphan designations were granted for N=195 unique conditions; N=328 designations were granted to non-FDA approved treatments or prophylaxis for N=159 unique conditions. After manual reconciliation of discrepancies between AI models, 92 conditions (57.9%) were confirmed to have at least one previously FDA-approved therapy or prophylaxis indicated for the condition of interest or associated side effect. Initial agreement between models was high (Cohen’s κ = 0.86, 95% CI: 0.72-0. 99), prior to reconciliation of 18 discrepant conditions. Among the N=67 rare diseases without current FDA-approved therapy, 19.4% (N=13) were diseases of the nervous system, followed by 14.9% (N=10) in endocrine and metabolic diseases, and 10.5% (N=7) in neoplasms. Among the rare diseases without current therapy, N=88 designations were granted and 65.9% were for biologics.
CONCLUSIONS: Nearly half of rare diseases with FDA treatment designations in 2025 lack existing FDA-approved treatments, underscoring a substantial unmet medical need.
METHODS: Using the U.S. Food and Drug Administration (FDA)’s orphan drug designation database, we identified orphan designations granted for the treatment or prevention of rare diseases in 2025 and restricted the sample to non-FDA-approved treatments. We used two AI-assisted tools to classify whether the designated conditions had existing FDA-approved therapies, and two researchers independently validated the classifications. Focusing on rare diseases without existing approved treatments, we characterized the orphan-designated treatments and therapeutic areas.
RESULTS: In 2025, N=389 orphan designations were granted for N=195 unique conditions; N=328 designations were granted to non-FDA approved treatments or prophylaxis for N=159 unique conditions. After manual reconciliation of discrepancies between AI models, 92 conditions (57.9%) were confirmed to have at least one previously FDA-approved therapy or prophylaxis indicated for the condition of interest or associated side effect. Initial agreement between models was high (Cohen’s κ = 0.86, 95% CI: 0.72-0. 99), prior to reconciliation of 18 discrepant conditions. Among the N=67 rare diseases without current FDA-approved therapy, 19.4% (N=13) were diseases of the nervous system, followed by 14.9% (N=10) in endocrine and metabolic diseases, and 10.5% (N=7) in neoplasms. Among the rare diseases without current therapy, N=88 designations were granted and 65.9% were for biologics.
CONCLUSIONS: Nearly half of rare diseases with FDA treatment designations in 2025 lack existing FDA-approved treatments, underscoring a substantial unmet medical need.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HPR143
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling, Health Disparities & Equity
Disease
SDC: Rare & Orphan Diseases