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Increasingly, non\u2010hemophilia bleeding disorders and a broader demographic (females, children, and infants) are being incorporated into study populations. Ongoing clinical trials broadly address three themes: (1) indication expansion for licensed therapeutics in previously uninvestigated patient subgroups or clinical scenarios, (2) evaluation of efficacy and safety among other bleeding disorders such as von Willebrand disease, platelet function defects, and rare clotting factor deficiencies, and (3) longitudinal assessment of approved treatments particularly with regard to longer\u2010term efficacy outcomes such as musculoskeletal health and treatment\u2010specific safety outcomes including thrombotic risk and liver health. With these new prophylaxis modalities, providers must have a nuanced understanding of each therapy's mechanism of action, advantages, side effect profile, therapeutic limitations, and impact on hemostasis and laboratory monitoring. Treatment is no longer \u201cone size fits all.\u201d Rather, management is tailored to individual needs and preferences. Here, we review active investigational trials and highlight promising approaches in preclinical development, expanding the innovative, complex landscape of inherited bleeding disorders therapeutics.<\/jats:p>","DOI":"10.1002\/ajh.27602","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T03:54:39Z","timestamp":1738641279000},"page":"666-684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["2025 Clinical Trials Update on Hemophilia, <scp>VWD<\/scp>, and Rare Inherited Bleeding Disorders"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2978-3585","authenticated-orcid":false,"given":"Debbie","family":"Jiang","sequence":"first","affiliation":[{"name":"Hematology Division Massachusetts General Hospital  Boston Massachusetts 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