25 Years of the Orphan Drug Act: Analysis of the orphan drugs designated and approved by the US FDA between 1983 and 2007

OBJECTIVES: In 1983 the Orphan Drug Act provided incentives to develop new drugs for rare diseases (orphan drug-OD). The objectives of this study were to analyze the characteristics of OD designations and approvals, and to compare the patent and exclusivity time of the ODs with the non-OD approved by the U.S. FDA in the period 1983-2007.

METHODS: The study included all OD designations and approvals, and all new molecular entities (NMEs) approved by the FDA in the study period. Data derived from the FDA. Differences between group means and between proportions were assessed using the t-test and chi-square test, respectively.

RESULTS: The FDA granted 1,749 OD designations and 318 OD approvals. Designations were granted to 799 sponsors and referred to 1,192 different products. Main orphan diseases/indications targeted were cancer (32%), transplants (5%) and HIV/AIDS (5%). The approval rate for OD designations was 10% for the 511 companies that had 1 OD designation and 32% for the 23 companies that had more than 10 OD designations.

The FDA approved 635 NMEs; 28% of the NMEs had at least 1 OD designation and 18% of the NMEs were first approved for an orphan indication. Sponsors of OD NMEs were more likely to be US companies than non-US companies (64.0% vs. 54.4%) (p<.05) and to have approved one NME vs. multiple NMEs (28.3% vs.14.2%) (p<.001). The average time from OD designation to OD NME approval was 3.4 years.

More OD NMEs did not have patents listed in the FDA Orange Book than non-OD NMEs (37.8% vs. 17.2%) (p<.001). Differences in effective patent time were not statistically significant. OD NMEs had an average of 10.94±4.42 years of effective patent life for the first patent vs. 10.81±4.29 years for non-OD NMEs. OD NMEs had an average of 14.17±4.52 years of effective patent life for the last patent vs. 14.91±4.91 years for non-OD NMEs. Significantly (p<0.001) more OD NMEs had exclusivity time that was longer than the effective patent time than non-ODs (42% vs. 16%) (p<0.001). OD NMEs had less generic competition than non-OD NMEs (18.0% vs. 29.6%) (p<.05).

CONCLUSIONS: The approval rate of OD designations was correlated to the total number of OD designations made by a company. US companies and companies with only one OD designation were more likely to use the OD regulatory provision. OD NMEs had similar effective patent time, more exclusivity time protection and less generic competition than non-OD NMEs.