Critical analysis of withdrawn drug applications in marketing authorization procedures of the European Medicines Agency (EMA) 2006-2024.

Withdrawn drug applications (WDAs) are drug approval applications withdrawn by the applicant before the European Medicines Agency (EMA) has made a final decision. To better understand the main reasons for the emergence of WDAs, this study critically analyzes all WDAs in the period from 2006 to 2024. The data analysis is based on the 330 WDAs published by the EMA during the period mentioned above. Various parameters were analyzed, such as active substances, therapeutic subgroups and objections raised by the EMA. The most common therapeutic subgroups are antineoplastic agents (N = 80), followed by immunosuppressants (N = 23). Most drug approval applications are for initial approval (N = 244; 73.9%), supported by a single key clinical trial. In 77.3% (N = 255) of cases, the key clinical trials included a control arm (reference drug and/or placebo). In 69.7% (N = 230) of cases, no initial marketing authorization recommendation was made by the EMA's Committee for Medicinal Products for Human Use (CHMP). The most common reason for this was concerns about clinical efficacy (33.46%; N = 348), partly due to inadequate clinical trial design. A major reason for the accumulation of WDAs in the antineoplastic agents group is presumably the high demand for supply and the resulting economic potential of this drug group. The present analysis may contribute to the identification of obstacles and the resulting potential for optimization in the EMA's drug approval procedures.