FDA Orphan Designations, Approvals, and Regulatory Review Time since the Enactment of the Orphan Drug Act (1983)

Abstract

Background Drug approvals for rare diseases and conditions have increased significantly since the Orphan Drug Act (ODA) enactment in 1983. Yet, the factors explaining the increase in orphan drug approvals are poorly understood. This study assessed the characteristics of orphan drug designations and approvals and evaluated factors associated with the approval of orphan designations and the time lag between orphan designation and approval in the US from 1983 to 2021. Methods Data were collected from the FDA Orphan Drug Product Designations and Approvals database of the FDA Office of Orphan Products Development. We conducted regression analyses to ascertain factors associated with the likelihood of approval of an orphan designation and the time lag between orphan designation and approval after controlling for the orphan drug designation date. Results As of December 31, 2021, the FDA had granted 6,137 orphan designations and 1,045 (17.0%) orphan drug approvals of which 285 drugs (27.3%) were first approved for non-rare diseases and conditions. FDA granted an annual average of 90.4 orphan designations since implementing the Orphan Drug Modernization Plan (ODMP) through December 31, 2021. After controlling for the orphan drug designation date, drugs with prior orphan designations, drugs sponsored by companies that had already obtained orphan approval, and drugs with orphan pediatric indications had a greater likelihood of approval. The time lag from orphan designation to approval was inversely associated with the number of prior orphan approvals of the sponsored company and the implementation of the ODMP. Conclusions The number of FDA approved orphan drugs increased significantly after enacting the Orphan Drug Act of 1983. The likelihood of approval of an orphan drug designation and the time lag from orphan designation to approval was significantly associated with enacted regulation, the experience of the sponsor companies obtaining orphan approval, the patient population indication, and previous designation for other orphan indications. There is a significant reduction in the time lag between orphan drug designation and approval after ODMP enactment.