The U.S. Food and Drug Administration signaled a major shift in approval standards, saying a single well‑controlled trial plus confirmatory evidence can suffice for approval in many cases. The policy change — framed in a New England Journal of Medicine article by agency leaders — aims to lower development costs and speed access to medicines. Separately the FDA released draft guidance formalizing the “plausible mechanism” pathway to accelerate individualized and ultrarare therapies where randomized trials aren’t feasible. The draft outlines evidentiary expectations for bespoke gene‑ and cell‑based products and clarifies manufacturing and mechanistic data that sponsors should present. Together, the moves recalibrate evidentiary thresholds for drug approvals and signal the regulator’s willingness to embrace alternative clinical paradigms for rare and rapidly evolving modalities.