Landmark upcoming FDA approval decisions will test the agency's commitment to biomarker-based accelerated approvals for orphan drugs, potentially reshaping rare disease regulatory frameworks. Concurrently, complexities within the evolving FDA leadership and policy environment create unpredictability impacting biopharma firms differently, with larger pharmaceutical companies reportedly gaining competitive advantages over smaller biotech innovators. These shifts underline both opportunities and uncertainties facing the industry in navigating regulatory landscapes for novel therapies.