FDA officials Vinay Prasad and Martin Makary published a ‘plausible mechanism pathway’ proposing expedited approval routes for bespoke medicines in rare diseases, drawing praise and criticism from regulators and developers. The pathway—rooted in case examples like the personalized in‑vivo CRISPR treatment for infant “KJ”—argues that molecularly targeted, n‑of‑1 therapies could be cleared based on mechanistic evidence when randomized trials are impractical. Thought leaders at an FDA panel and academic experts noted the framework addresses unmet needs but leaves open questions about evidentiary standards, patient protections and post‑market follow‑up.