FDA orphan drug designations for lysosomal storage disorders - a cross-sectional analysis.

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.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SG, SK, and CS have no potential conflicts of interest to declare with respect to the research, authorship, and/or publication of this article. KM has served as investigator in clinical trials conducted by Emalex, Gedeon Richter, Lundbeck, Shire, Sunovion and Teva, plus in European Union funded projects. GFH received lecturing fees from Danone and Takeda. EM has received honoraria and/or consulting fees from Actelion, Alexion, BioMarin, Orphazyme, Sanofi Genzyme, and Shire. MR received consultancy fees or research grants from Alexion, GSK, Oxyrane and Shire. EM is managing partner of SphinCS GmbH, a private clinical research institute, which had research grants from Sanofi Genzyme, Takeda, Alexion, Orphazyme and Idorsia. This does not alter our adherence to PLOS ONE policies on sharing data and materials.