First-In-Class Drugs Experienced Different Regulatory Treatment In The US And Europe.

Abstract

First-in-class drugs can be highly innovative because of their novel mechanisms of action, but they also carry uncertainty in the absence of clinical experience. To understand how such drugs advance through development to enter the market, we investigated Food and Drug Administration (FDA) approval data for 186 first-in-class drugs (2013-23) and data for 121 drugs approved by both the FDA and the European Medicines Agency (EMA; 2013-22), focusing on review durations, expedited program use, and characteristics of pivotal efficacy trials. The FDA applied substantial regulatory flexibility to first-in-class drugs, with 50 percent lacking clinical endpoints and 30 percent lacking blinding and comparator drugs in the pivotal trials. This flexibility was particularly evident in cancer drugs, for which up to 90 percent lacked clinical endpoints and blinding. The FDA designated 81 percent of first-in-class drugs for expedited programs compared with 30 percent designated by the EMA. Review durations varied by therapeutic area, ranging from 7.7 months to 14.5 months at the FDA, and were slightly slower at the EMA. Regulators need to carefully balance flexibilities with rigorous assessments of evidence for first-in-class drugs.