The U.S. Food and Drug Administration announced a formal shift away from the historic default requiring two pivotal trials for drug approvals, signaling that one well‑controlled study plus confirmatory evidence can support licensure. The policy change was articulated in a New England Journal of Medicine piece authored by FDA leadership and follows growing industry calls to modernize evidentiary standards. Separately, the agency published draft guidance detailing a 'plausible mechanism' pathway for individualized therapies — a framework aimed at accelerating bespoke cell and gene treatments for ultra‑rare conditions where randomized trials are infeasible. The guidance outlines evidentiary expectations and manufacturing considerations sponsors should meet for individualized products. Regulators framed the moves as efforts to reduce development time and costs while preserving safety and scientific rigor. The combined policy shifts are likely to affect trial design, finance planning, and go‑to‑market timelines for developers of precision, rare‑disease, and advanced biotherapeutics.