U.S. regulators told uniQure that data from its single‑arm AMT‑130 program are insufficient and “strongly recommended” a randomized, double‑blind, sham surgery–controlled study before the company can file for approval. The FDA request, communicated after review meetings, forces uniQure to consider a prospective trial that could add two to three years to development timelines and raise complex ethical and operational questions. The recommendation targets AMT‑130, uniQure’s in‑brain gene therapy for Huntington’s disease, and follows agency concerns about reliance on external and historical controls. A sham surgery control involves randomly assigning patients to a simulated surgical procedure without therapeutic delivery to preserve blinding; regulators view it as the most rigorous method to demonstrate benefit when objective endpoints are sparse. UniQure indicated it will seek further FDA guidance on trial design and timing. The agency’s stance underscores regulators’ insistence on randomized evidence for invasive, one‑time central nervous system interventions, even for rare neurodegenerative indications.