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The purpose of this study is to assess the impact of the US orphan drug act on AATD by providing a quantitative clinical-regulatory insight into the status of FDA orphan drug approvals and designations for compounds intended to treat AATD. This is across-sectional analysis of the FDA database for orphan drug designations. Primary endpoint: orphan drug approvals. Secondary endpoint: orphan drug designations by the FDA. Close of database\u00a0was 16 July 2021. STROBE criteria were respected. Primary\u00a0outcome: one compound, alpha-1-proteinase inhibitor (human) was approved as an orphan drug in 1987 with market exclusivity until 1994. Secondary\u00a0outcome: sixteen compounds received FDA orphan drug designation including protein, anti-inflammatory, mucolytic, gene, or cell therapy. Drug development activities in AATD were comparable to other rare conditions and led to the FDA-approval of one compound, based on a relatively simple technological platform. The current unmet medical need to be addressed are extrapulmonary manifestations, in this case the AATD-associated liver disease. Orphan drug development is actually focusing on (1) diversified recombinant AAT production platforms, and (2) innovative gene therapies, which may encompass a more holistic therapeutic approach.<\/jats:p>","DOI":"10.1038\/s41598-022-19707-2","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T11:04:31Z","timestamp":1663239871000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Orphan drug development in alpha-1\u00a0antitypsin deficiency"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-7586","authenticated-orcid":false,"given":"Franziska C.","family":"Trudzinski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ada","family":"Presotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix J. 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