A BioCentury analysis identified a pattern of recent reversals and shifting positions by the FDA that have generated uncertainty for developers of rare‑disease therapies. The report cites multiple cases where earlier guidance or signals from the agency were altered, prompting questions about evidentiary expectations and predictability during regulatory review. Stakeholders told BioCentury that changing standards increase development risk, complicate trial design, and may lengthen time to market for therapies addressing small populations. The piece underscores the intensifying scrutiny on regulatory decision‑making and the strategic implications for biotech companies targeting orphan and rare indications.