The FDA’s move to adopt a default of relying on one adequate, well‑controlled trial for marketing authorization is provoking industry debate about global consequences and payer expectations. A New England Journal of Medicine piece by FDA leadership outlined the policy intent to accelerate drug development, but analysts warned it may clash with international norms and reimbursement standards. Separately, FDA Commissioner Marty Makary defended recent rejections of rare disease therapies on CNBC, arguing some high‑profile programs lacked demonstrable benefit—comments that fueled pushback from advocates and firms that cite opaque regulatory shifts. The exchanges underscore mounting tension between speed, evidentiary rigor and political scrutiny in rare disease review pathways.