The “Makary Doctrine” and the Billion-Dollar Impact of the Single-Trial Default
In December 2025, FDA Commissioner Dr. Marty Makary announced a policy shift that biopharma consultants have termed a “regulatory acceleration warhead.” By moving the agency’s default requirement from two adequate and well-controlled Phase 3 clinical trials to a single pivotal trial, the FDA is effectively rewriting the rules of engagement for approximately one-third of the drug development pipeline.While the agency has long exercised flexibility for rare diseases and oncology, this new directive targets the mass-market indications—Psychiatry, Cardiology, and Dermatology—that have historically been burdened by the expensive “Rule of Two.”
