Therapies for inborn errors of metabolism: what has the orphan drug act delivered?
OBJECTIVE
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).


METHODS
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.


RESULTS
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: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003).


CONCLUSIONS
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.
Talele
Sonali S
SS
Food and Drug Administration, Office of Orphan Products Development, Silver Spring, MD 20993-0002, USA.
Xu
Kui
K
Pariser
Anne R
AR
Braun
M Miles
MM
Farag-El-Massah
Sheiren
S
Phillips
M Ian
MI
Thompson
Barry H
BH
Coté
Timothy R
TR
D002648:Child; D002675:Child, Preschool; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions; D015507:Drugs, Investigational / Q000008:administration & dosage*; D005260:Female; D005544:Forecasting; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000188:drug therapy*; D020380:Needs Assessment; D009965:Orphan Drug Production / Q000331:legislation & jurisprudence* / Q000706:statistics & numerical data; D014481:United States; D014486:United States Food and Drug Administration
D015507:Drugs, Investigational