The FDA signaled it is rethinking how it evaluates rare-disease trial criteria, including endpoint selection and the amount of efficacy and safety evidence required for approval. As more therapies reach the agency for rare indications, FDA called for outside input on what “sufficient” data should look like. The request reflects ongoing pressure across the rare disease space to balance accelerated pathways with rigorous demonstration of benefit. Endpoint selection is particularly sensitive in smaller populations where natural history variability and feasibility constraints complicate traditional trial designs. For sponsors, the process could affect future development strategies around study design, statistical powering, and what claims can be supported by available controls and biomarker-linked outcomes.