Evidence available and used by the Food and Drug Administration for the approval of orphan and nonorphan drugs.

Abstract

There are substantial financial incentives to develop orphan drugs for rare diseases, but concerns about the quality and volume of supporting evidence have emerged. We compare evidence used to evaluate orphan and nonorphan drugs approved by the Food and Drug Administration (FDA) between 2016 and 2023. This retrospective cross-sectional analysis utilizes FDA data on approvals and study information from ClinicalTrials.gov to compare characteristics of studies relevant to orphan and nonorphan drugs approved between 2016 and 2023. Of the 368 total drugs approved, 50% were orphan drugs. The FDA-approved drugs based on significantly fewer studies for orphan (1.5 studies/drug) compared to nonorphan (2.4 studies/drug). Additionally, a significantly lower proportion of studies were completed before FDA approval for orphan drugs (25% vs 41%). Orphan drugs were significantly less likely to be evaluated in randomized clinical trials (RCTs) (34% vs 63%). Of these RCTs, there were significantly fewer completed before approval (40% vs 54%) and that had results posted (35% vs 53%). There was a significant difference in the available evidence for orphan and nonorphan drugs. As new legislation like Cures 2.0 is developed, it is critical to examine the balance between an expedited approval timeline and the standard of clinical evidence.