FDA reversed course in an ultra-rare disease filing decision, clearing Saol to resubmit an NDA rather than run a new clinical trial. The shift is described as another “Makary era” reversal, continuing a pattern of regulatory outcomes changing expectations for rare-disease development. For rare-disease developers, resubmission pathways can materially affect timelines, trial costs, and the probability of reaching registrational milestones under accelerated or expedited frameworks. The update signals how quickly agency positions can evolve, particularly where evidence packages and trial design requirements are under dispute. Biotech teams are likely to treat the Saol outcome as a guidance datapoint when negotiating end-of-phase and NDA evidence expectations in similar rare-disease contexts.