Orphan Drugs for Metabolic Disorders by the Numbers

Between 1983 and 2014, a total of 45 orphan drugs have been approved for rare metabolic disorders (as defined by ICD-10 Version:2015 disease classification system), representing 9.4% of all orphan drug approvals (481) during this time period. This involves approvals in 12 metabolic disorder categories and for 23* individual metabolic disorders (click on link).

A few noteworthy observations are as follows:

1) While the majority of rare metabolic disorders have only one orphan drug approval each, two disorders have 6 approvals (Gaucher Disease Type 1, Hypercalcemia), one disorder has 5 (Hyperammonemia); two disorders have 3 (Cystinosis, Cystic Fibrosis), and four disorders have 2 each (Pompe Disease, Homozygous Familial Hypercholesterolemia, Wilson Disease, Hemosiderosis).

2) Analysis of lengths of registration interests for individual metabolic disorders (duration from first approval date to latest approval date) shows that six of these had > 10 years of registration interests each. As expected, these are typically those disorders with several approvals each, i.e., Hypercalcemia (27 years, 7 months), Cystinosis (24 years, 8 months), Gaucher Disease Type 1 (23 years, 4 months), Hyperammonemia (23 years, 1 month), Cystic Fibrosis (18 years, 1 month), and Wilson Disease (11 years, 2 months).

3) In contrast to drug approvals for common diseases, which have a variety of mechanisms of action, e.g., agonism, antagonism, enzyme inhibition and replacement, orphan drugs for rare metabolic disorders have a significant number of approvals involving enzyme replacement therapies, or 14 of the 45 approvals, or almost one-third (31.1%).

4) Considering the relatively recent activities on orphan drug development and approvals, initiated by the passage of the Orphan Drug Act in 1983, a question arises regarding what key differences might exist in drug discovery and development considerations between drugs for common diseases and rare diseases, in addition to issues like number of patients affected, trial designs, commercial projections, and drug costs. One such potential issue involves issues like development success rates and attrition, considering possibly greater knowledge and certainty about disease-causing etiologies, at least for some metabolic disorders; however, we are not aware of development attrition assessment for rare metabolic disorders or other rare diseases.

* Note the two ICD-10 subcategories for Cystic Fibrosis are combined.

Refer to report on Progression of Orphan Therapeutics: Metabolic Disorders available under Reports on this website.