The U.S. Food and Drug Administration announced a policy shift allowing approval on the basis of one well‑controlled trial plus confirmatory evidence, a change framed as an end to the longstanding “two‑trial” default. Agency leaders argued modern analytics and richer biological endpoints can supply the necessary confidence in efficacy and safety. In parallel the agency published draft guidance establishing a 'plausible mechanism' pathway to speed individualized cell and gene therapies for ultrarare conditions—pairing the single‑trial flexibility with a clearer route for bespoke development programs.