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A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act
Open accessAbstract
Background: Rare diseases affect more than 30 million Americans. The passage of the Orphan Drug Act (ODA) in the United States in 1983 represented a launching point for a rare disease drug development revolution for these patients. Financial incentives provided by the ODA through its Orphan Drug Designation Program, in addition to remarkable scientific advances over the past 40 years, have led to hundreds of drug approvals for rare diseases. Our research examines the rare diseases that have been targeted by orphan drug designations and subsequent approvals since the law was enacted. Methods: Using an internal FDA database, we classified and analyzed all orphan drug designations and approvals from 1983 to 2022 by disease and therapeutic area. Results: Over the 40 years of the ODA, 6,340 orphan drug designations were granted, representing drug development for 1,079 rare diseases. Additionally, 882 of those designations resulted in at least one FDA approval for use in 392 rare diseases. Much of this development has been concentrated in oncology as seven of the top ten most designated and approved diseases were rare cancers. Conclusions: Researchers have estimated that there may be 7000–10,000 rare diseases that have been identified and described. Based on our study, we can conclude that around 5% of rare diseases have an FDA-approved drug and up to 15% of rare diseases have at least one drug that has been developed and shown promise in their treatment, diagnosis or prevention. Funding of basic and translational science for rare disease drug development should continue in order to bring therapies to the millions of affected patients who remain without treatment options.
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“Moreover, around 95% of rare diseases have no FDA-approved drugs and up to 85% of rare diseases do not have even one drug developed that would show promise in rare disease treatment, diagnosis or prevention21.”
From A foundation model for clinician-centered drug repurposing (2024) · cites this paper as [21]
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“For instance, the molecular basis of many rare diseases remains poorly understood21.”
From A foundation model for clinician-centered drug repurposing (2024) · cites this paper as [21]
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Cites
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How many rare diseases are there?
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“Now, four decades later, hundreds of “orphan” drugs have been approved for use in the 7000–10,000 diseases and conditions that are considered rare.[3].”
BackgroundMondo: Unifying diseases for the world, by the world
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Self-citationCFTR modulator therapies – Effect on life expectancy in people with cystic fibrosis
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Investigating the landscape of US orphan product approvals
Miller, K. L., & Lanthier, M. L. (2018) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0930-3 · Cited by 52
Self-citationShould rare diseases get special treatment?
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A foundation model for clinician-centered drug repurposing
Huang, K., Chandak, P., Wang, Q., Havaldar, S., Vaid, A., Leskovec, J., Nadkarni, G. N., Glicksberg, B. S., Gehlenborg, N., & Zitnik, M. (2024) · Nature Medicine · doi:10.1038/s41591-024-03233-x · Cited by 249
“For instance, the molecular basis of many rare diseases remains poorly understood 21 .”
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A roadmap for affordable genetic medicines
Kliegman, M., Zaghlula, M., Abrahamson, S. L., Esensten, J. H., Wilson, R. C., Urnov, F. D., & Doudna, J. A. (2024) · Nature · doi:10.1038/s41586-024-07800-7 · Cited by 69
Drug repurposing for Alzheimer’s disease and other neurodegenerative disorders
Cummings, J. L., Zhou, Y., Stone, A. V., Cammann, D., Tonegawa‐Kuji, R., Cacho, J. R. F., & Cheng, F. (2025) · Nature Communications · doi:10.1038/s41467-025-56690-4 · Cited by 80
Domaradzki, J., & Walkowiak, D. (2024) · Scientific Reports · doi:10.1038/s41598-024-63962-4 · Cited by 31
Metadata
- Authors
- Fermaglich, L. J., & Miller, K. L.
- Affiliations
- United States Food and Drug Administration (US)
- Corresponding author
- Fermaglich, Lewis J.
- Venue
- Orphanet Journal of Rare Diseases
- Published
- 2023-06-23
- Volume
- 18
- Issue
- 1
- Pages
- 163-163
- ISSN
- 1750-1172 (ISSN-L)
- PMC
- PMC10290406
- OpenAlex
- W4381839562
- Cited by
- 134
- References
- 14
- Citations by year
- 2026: 41 · 2025: 58 · 2024: 28 · 2023: 7
- FWCI
- 27.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Nursing › Issues, ethics and legal aspects › Biomedical Ethics and Regulation
- Keywords
- rare diseases, orphan drugs, Orphan Drug Act, orphan drug designation, drug approval, rare tumor, anticancer drug development, therapeutic areas, FDA drug approval, rare disease drug development
- MeSH terms
- Humans, Neoplasms, Orphan Drug Production, United States, United States Food and Drug Administration, Drug Approval, Rare Diseases
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