OBJECTIVES: The Orphan Drug Act of 1983 provides branded drugs with extended exclusivity up to 7 years per approved rare disease indication. There is concern that the Act may negatively impact long-term availability of affordable alternatives because some manufacturers apply for numerous orphan approvals to prevent competition for rare disease indications. Our objective was to determine the amount of additional time that approved orphan drugs have been able to maintain market exclusivity through multiple rare disease indications.

METHODS: We conducted a retrospective cohort analysis of FDA Orphan Drug Designations and Approvals between 1983-2017. The mean time of exclusivity gained in years per additional orphan drug approval was calculated to determine whether certain specialty drugs for rare diseases were gaining extensive amounts of exclusivity with multiple orphan approvals. A fixed-effects model regressed the extended duration of exclusivity per additional approval over time, controlling potential policy interruptions over 34 years.

RESULTS: We identified 413 drugs approved for 615 rare disease indications in the U.S. under the Orphan Drug Act. Of these drugs, those approved for a second orphan indication had 4.7 years of average increase in market exclusivity (p<0.05) beyond the initial 7 years. The third approval gained 3.1 additional years; the fourth gained 2.7 additional years; and the fifth gained 2.9 additional years (p<0.05). Taken together, five orphan drug approvals resulted in an average of 13.4 additional years of market exclusivity across all indications. Since the beginning of the Act, exclusivity has increased in all orphan drugs over time (p<0.01).

CONCLUSIONS: The Orphan Drug Act may be used to help manufacturers maintain branded status longer than initial periods and may contribute to increasing drug costs. Limiting the number of additional exclusivity periods a single drug can receive could increase access and affordability, and motivate competition among rare disease treatments.