Top FDA officials published a New England Journal of Medicine perspective making a single well‑controlled pivotal trial the agency’s new “default” standard for drug approvals, while asking sponsors to supplement dossiers with confirmatory mechanistic or supportive evidence. The move—authored by FDA leaders—makes explicit a policy the agency had exercised discretion over in recent years. The paper outlines circumstances in which the FDA will still require two trials, but stresses that mechanistic data, related‑indication results, animal models or robust real‑world evidence can function as “confirmative” support alongside one pivotal outcome. The change is pitched as a way to lower late‑stage costs and accelerate patient access while retaining flexibility to request more data where risk or uncertainty is high. Industry reactions were mixed: developers hailed the potential to compress timelines and reduce trial burden, while some experts warned about statistical robustness and the risk of approving therapies on limited evidence—particularly where surrogate endpoints are used. What’s next: sponsors will need to redesign submission strategies to pair a single pivotal trial with layered confirmatory evidence; investors and litigation watchers will watch how the new default is operationalized in review letters and advisory committee decisions.