Endnotes 1. Nguengang Wakap, S., Lambert, D. M., Olry, A., et al. (2020). Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database. European Journal of Human Genetics, 28, 165–173. https://doi.org/10.1038/s41431- 019-0508-0 2. IQVIA, & Chiesi Global Rare Diseases. (2022). The burden of rare diseases: An economic evaluation. https:// chiesirarediseases.com/assets/pdf/chiesiglobalrarediseases.whitepaper-feb.-2022_production-proof.pdf 3. United Nations General Assembly. (2022, January 5). Resolution adopted by the General Assembly on 16 December 2021. https://digitallibrary.un.org/record/3953765?ln=en&v=pdf 4. World Health Organization (WHO). (2025, May 27). Rare diseases: A global health priority for equity and inclusion. https:// apps.who.int/gb/ebwha/pdf_files/WHA78/A78_R11-en.pdf 5. Estimates for the number of rare diseases vary due to differences in classification systems and disease definitions. Despite efforts to harmonize nomenclatures, multiple ontologies remain in use, leading to varying methodologies for what counts as a distinct rare disease – and in some cases, higher estimates. 6. Wang, C. M., Whiting, A. H., Rath, A., et al. (2024). Operational description of rare diseases: A reference to improve the recognition and visibility of rare diseases. Orphanet Journal of Rare Diseases, 19, 334. https://doi.org/10.1186/s13023- 024-03322-7 7. Rohani-Montez, S. C., Bomberger, J., Zhang, C., et al. (2023). Educational needs in diagnosing rare diseases: A multinational, multispecialty clinician survey. Genetics in Medicine Open, 1, 100808. https://doi.org/10.1016/j. gimo.2023.100808 8. Faye, F., Crocione, C., Anido de Peña, R., et al. (2024). Time to diagnosis and determinants of diagnostic delays of people living with a rare disease: A Rare Barometer retrospective patient survey. European Journal of Human Genetics. Advance online publication. https://doi.org/10.21203/rs.3.rs-3787868/v1 9. IQVIA, & Chiesi Global Rare Diseases. (2022). The burden of rare diseases: An economic evaluation. https:// chiesirarediseases.com/assets/pdf/chiesiglobalrarediseases.whitepaper-feb.-2022_production-proof.pdf 10. EveryLife Foundation for Rare Diseases. (2021). The national economic burden of rare disease study. https:// everylifefoundation.org/wp-content/uploads/2021/02/The_National_Economic_Burden_of_Rare_Disease_Study_ Summary_Report_February_2021.pdf 11. Charles River Associates (commissioned by Alexion, AstraZeneca Rare Disease). (2024). The economic cost of living with a rare disease across Europe. https://media.crai.com/wp-content/uploads/2024/10/28114611/CRA-Alexion-Quantifying- the-Burden-of-RD-in-Europe-Full-report-October2024.pdf 12. Charles River Associates (commissioned by Alexion, AstraZeneca Rare Disease). (2025). The economic cost of living with a rare disease in Japan. https://media.crai.com/wp-content/uploads/2025/05/23104824/CRA-Alexion-The-economic- cost-of-living-with-a-rare-disease-in-Japan-May2025.pdf 13. Copenhagen Economics (2025). Spending on orphan medicinal products across Europe: What drives it and is it sustainable? https://copenhageneconomics.com/wp-content/uploads/2025/09/Copenhagen-Economics_Spending-on- OMPs-across-Europe.pdf 14. Goldstein, J. L., & Brown, M. S. (2015). A century of cholesterol and coronaries: From plaques to genes to statins. Cell, 161(1), 161–172. https://doi.org/10.1016/j.cell.2015.01.036 15. Musunuru, K., Grandinette, S. A., Wang, X., et al. (2025). Patient-specific in vivo gene editing to treat a rare genetic disease. The New England Journal of Medicine, 392(22), 2235–2243. https://doi.org/10.1056/NEJMoa2504747 16. Keeley, J., Stroobach, A., Huston, M., et al. (2024). Pandemic preparedness needs for children with rare diseases and their families: A perspective of COVID-19 experiences. Rare, 2, 100039. https://www.sciencedirect.com/science/article/ pii/S295000872400022X 17. National Academies of Sciences, Engineering and Medicine. (2024). Regulatory processes for rare disease drugs in the United States and European Union: Flexibilities and collaborative opportunities. The National Academies Press. https://doi. org/10.17226/27968 18. Centre for Innovation in Regulatory Science (CIRS). (2024). Rare disease product approvals: The changing regulatory and HTA landscape between 2018–2022. https://cirsci.org/publications/posters/rare-disease-product-approvals-the- changing-regulatory-and-hta-landscape-between-2018-2022/ 19. Chan, C. H., Parker, S., & Pearce, D. A. (2023). The international rare disease research consortium (IRDiRC): Making rare disease research efforts more efficient and collaborative around the world. Rare Disease and Orphan Drugs Journal, 2 (28). http://dx.doi.org/10.20517/rdodj.2023.23 20. Wilkinson, M. D., Dumontier, M., Aalbersberg, I. J., et al. (2016). The FAIR guiding principles for scientific data management and stewardship. Scientific Data, 3, 160018. https://doi.org/10.1038/sdata.2016.18 Making Rare Diseases Count: How Better Data Can Unlock a Multitrillion-Dollar Opportunity 32

Making Rare Diseases Count 2026