The FDA introduced a new regulatory pathway called the "plausible mechanism pathway" published by FDA Commissioner Martin Makary and Center for Biologics Evaluation and Research Vinay Prasad in the New England Journal of Medicine on November 12, 2025.[1] This pathway is intended for personalized therapies in rare and serious diseases where traditional randomized clinical trials are not feasible.[1] The new regulatory pathway targets diseases with a known biological cause and has five key elements: identification of a specific molecular or cellular abnormality, a product targeting the underlying cause of the disease, a well-characterized course of the untreated disease, confirmation that the target has been successfully affected or edited, and improved clinical outcomes.[1][2] The FDA will accept evidence from animal models, non-animal-animal models, or clinical biopsies, and in some cases, evidence from the first patient.[4] This pathway represents a shift in the FDA's regulatory approach toward greater flexibility in the development of individualized therapies, particularly for fatal, rare, and serious childhood diseases without alternative treatment options.[1]