uniQure said the FDA reversed prior guidance and no longer considers Phase I/II data using an external control adequate to support a biologics license application for AMT‑130, its gene therapy for Huntington’s disease. The company said timing for a BLA submission is now unclear after a pre‑BLA meeting; AMT‑130 had shown large slowing of disease in a small high‑dose cohort. External controls are matched untreated cohorts used when randomized placebo arms are impractical. The announcement knocked more than half off uniQure’s market value, reflecting investor concern about both the data standard and regulatory predictability. The development comes as the FDA’s Center for Drug Evaluation and Research faces leadership turmoil: George Tidmarsh, the agency’s recently appointed CDER director, resigned after being placed on administrative leave amid a Department of Health and Human Services probe. Tidmarsh’s exit intensifies uncertainty about how the agency will apply standards for accelerated approvals and external‑control data. Together these events raise practical questions for other developers relying on historical or external‑control designs—firms now face added risk that prior agency alignments may change. uniQure said it will urgently engage with the FDA to define a path forward.