The FDA has introduced a new “plausible mechanism pathway” aimed at expediting approval of personalized therapies for rare diseases.
The approach, detailed in a Nov. 12 article in The New England Journal of Medicine by FDA Commissioner Marty Makary, MD, and Center for Biologics Evaluation and Research Director Vinay Prasad, MD, is designed for treatments targeting ultra-rare conditions for which randomized trials are not feasible. It requires therapies to act on a known biological mechanism and show clinical improvement in patients.
The model draws on cases such as KJ, who received a bespoke CRISPR therapy in May for CPS1 deficiency, a rare genetic disorder. His treatment led to measurable clinical improvements, Dr. Makary and Dr. Prasad wrote.
Approval under the pathway will require evidence of success in multiple patients treated with distinct personalized therapies. Drugmakers also must collect real-world safety and efficacy data after approval.
While initially focused on rare conditions, the FDA said the pathway could extend to diseases with significant unmet needs, though applicability in more complex cases remains uncertain.
