Bridging the translational gap in drug repurposing for rare diseases: clinical success versus regulatory conversion.

Abstract

Repurposing of drugs to treat rare diseases (RDs) is vital, but the translational gap between clinical evidence and regulatory approval remains unquantified. Analysis of 47 clinical trials showed that 66 % of completed studies met their primary or key secondary endpoints. Nevertheless, only 39 % achieved marketing authorization (MA) by at least one major regulatory agency (32 % by the European Medicines Agency [EMA], 32 % by the US Food and Drug Administration [FDA], and 24 % by both agencies). A marked 'Sponsor gap' exists: academics led 64 % of trials, yet industry drove 75 % (EMA) and 67 % (FDA) of regulatory successes. When looking at Marketing Authorization Holders (MAHs), industry sponsors held 100 % of EMA authorizations in this cohort. To bridge this translational divide, we propose a framework combining AI-driven screening and N-of-1 trials to optimize academic-industrial handoffs and harmonize regulatory pathways, accelerating approval for underserved patient populations.