FDA leaders have signaled a formal shift: the agency will default to accepting one well-controlled, adequately run pivotal trial as sufficient evidence for approval, augmented by “confirmative evidence” such as mechanistic data, related-indication results, or real-world evidence. The policy was outlined by senior FDA officials in a New England Journal of Medicine perspective and reiterated in agency statements, marking an explicit change from the longstanding two-trial expectation. Regulatory and industry sources say the move aims to lower development costs and accelerate approvals for precision medicines and other modern therapeutics. Officials maintain discretion to require additional studies when necessary. The change is expected to alter late-stage development planning and deal terms, with sponsors and investors recalibrating risk and evidence strategies.