{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:06:33Z","timestamp":1779138393810,"version":"3.51.4"},"reference-count":9,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7,1]]},"abstract":"\n OBJECTIVE:<\/jats:title>\n The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs).<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6\u201325.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003).<\/jats:p>\n <\/jats:sec>\n \n CONCLUSION:<\/jats:title>\n For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.<\/jats:p>\n <\/jats:sec>","DOI":"10.1542\/peds.2009-3246","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T00:54:36Z","timestamp":1277168076000},"page":"101-106","source":"Crossref","is-referenced-by-count":23,"title":["Therapies for Inborn Errors of Metabolism: What Has the Orphan Drug Act Delivered?"],"prefix":"10.1542","volume":"126","author":[{"given":"Sonali S.","family":"Talele","sequence":"first","affiliation":[{"name":"Office of Orphan Products Development and"},{"name":"Center for Rare Disease Therapies, Keck Graduate Institute, Claremont, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui","family":"Xu","sequence":"additional","affiliation":[{"name":"Office of Orphan Products Development and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne R.","family":"Pariser","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Products, Office of New Drugs, Food and Drug Administration, Silver Spring, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Miles","family":"Braun","sequence":"additional","affiliation":[{"name":"Office of Orphan Products Development and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheiren","family":"Farag-El-Massah","sequence":"additional","affiliation":[{"name":"Office of Orphan Products Development and"},{"name":"Department of Social and Administrative Pharmacy Program, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Ian","family":"Phillips","sequence":"additional","affiliation":[{"name":"Center for Rare Disease Therapies, Keck Graduate Institute, Claremont, California;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry H.","family":"Thompson","sequence":"additional","affiliation":[{"name":"American College of Medical Genetics, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R.","family":"Cot\u00e9","sequence":"additional","affiliation":[{"name":"Office of Orphan Products Development and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2010,7,1]]},"reference":[{"key":"2021120820002706900_B1","unstructured":"Food and Drug Administration. Orphan Drug Act. Available at: www.fda.gov\/ForIndustry\/DevelopingProductsforRareDiseasesConditions\/Overview\/ucm119477.htm. Accessed June 27, 2009"},{"key":"2021120820002706900_B2","unstructured":"Food and Drug Administration. Overview: purpose of the Orphan Products Program. Available at: www.fda.gov\/ForIndustry\/DevelopingProductsforRareDiseasesConditions\/Overview\/default.htm. Accessed June 27, 2009"},{"key":"2021120820002706900_B3","unstructured":"Food and Drug Administration. Investigational new drug (IND) or device exemption (IDE) process (CBER). Available at: www.fda.gov\/BiologicsBloodVaccines\/DevelopmentApprovalProcess\/InvestigationalNewDrugINDorDeviceExemptionIDEProcess\/default.htm. Accessed July 24, 2009"},{"issue":"6","key":"2021120820002706900_B4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nrg1880","article-title":"Inborn errors of metabolism: the flux from Mendelian to complex diseases","volume":"7","author":"Lanpher","year":"2006","journal-title":"Nat Rev Genet"},{"key":"2021120820002706900_B5","unstructured":"Weiner\u2008DL\n . Pediatrics, inborn errors of metabolism. Available at: http:\/\/emedicine.medscape.com\/article\/804757-overview. Accessed July 20, 2009"},{"key":"2021120820002706900_B6","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-540-28785-8","volume-title":"Inborn Metabolic Diseases: Diagnosis and Treatment","author":"Fernandes","year":"2006"},{"issue":"2\u20133","key":"2021120820002706900_B7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10545-006-0358-0","article-title":"Clinical approach to treatable inborn metabolic diseases: an introduction","volume":"29","author":"Saudubray","year":"2006","journal-title":"J Inherit Metab Dis"},{"issue":"5","key":"2021120820002706900_B8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00228-007-0454-6","article-title":"Predictors of orphan drug approval in the European Union","volume":"64","author":"Heemstra","year":"2008","journal-title":"Eur J Clin Pharmacol"},{"issue":"23\u201324","key":"2021120820002706900_B9","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.drudis.2009.09.008","article-title":"Translation of rare disease research into orphan drug development: disease matters","volume":"14","author":"Heemstra","year":"2009","journal-title":"Drug Discov Today"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/126\/1\/101\/1050544\/zpe00710000101.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/126\/1\/101\/1050544\/zpe00710000101.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T23:16:21Z","timestamp":1639005381000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/126\/1\/101\/68328\/Therapies-for-Inborn-Errors-of-Metabolism-What-Has"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,7,1]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2010,7,1]]},"published-print":{"date-parts":[[2010,7,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2009-3246","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,7,1]]}}}