FDA orphan drug designations for lysosomal storage disorders

• Verfasst von: Garbade, Sven [VerfasserIn]
• Verfasst von: Zielonka, Matthias [VerfasserIn]
• Verfasst von: Mechler, Konstantin [VerfasserIn]
• Verfasst von: Kölker, Stefan [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Staufner, Christian [VerfasserIn]
• Verfasst von: Mengel, Eugen [VerfasserIn]
• Verfasst von: Ries, Markus [VerfasserIn]
• Titel: FDA orphan drug designations for lysosomal storage disorders
• Titelzusatz: a cross-sectional analysis
• Verf.angabe: Sven F. Garbade, Matthias Zielonka, Konstantin Mechler, Stefan Kölker, Georg F. Hoffmann, Christian Staufner, Eugen Mengel, Markus Ries
• E-Jahr: 2020
• Jahr: April 8, 2020
• Fussnoten: Gesehen am 02.07.2020
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2020
• Band/Heft Quelle: 15(2020,4) Artikel-Nummer e0230898, 12 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0230898
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1703404297

Abstract

Purpose - To provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat lysosomal storage disorders (LSDs). - - Methods - Assessment of the drug pipeline through analysis of the FDA database for orphan drug designations with descriptive and comparative statistics. - - Results - Between 1983 and 2019, 124 orphan drug designations were granted by the FDA for compounds intended to treat 28 lysosomal storage diseases. Orphan drug designations focused on Gaucher disease (N = 16), Pompe disease (N = 16), Fabry disease (N = 10), MPS II (N = 10), MPS I (N = 9), and MPS IIIA (N = 9), and included enzyme replacement therapies, gene therapies, and small molecules, and others. Twenty-three orphan drugs were approved for the treatment of 11 LSDs. Gaucher disease (N = 6), cystinosis (N = 5), Pompe disease (N = 3), and Fabry disease (N = 2) had multiple approvals, CLN2, LAL-D, MPS I, II, IVA, VI, and VII one approval each. This is an increase of nine more approved drugs and four more treatable LSDs (CLN2, MPS VII, LAL-D, and MPS IVA) since 2013. Mean time between orphan drug designation and FDA approval was 89.7 SD 55.00 (range 8-203, N = 23) months. - - Conclusions - The drug development pipeline for LSDs is growing and evolving, with increased focus on diverse small-molecule targets and gene therapy. CLN2 was the first and only LSD with an approved therapy directly targeted to the brain. Newly approved products included “me-too”-enzymes and innovative compounds such as the first pharmacological chaperone for the treatment of Fabry disease.