The U.S. FDA told uniQure to conduct a prospective, randomized, double‑blind, sham surgery‑controlled study to support marketing of AMT‑130, an AAV‑based gene‑editing therapy for Huntington’s disease. The agency concluded Phase I/II data compared to external controls are insufficient to establish effectiveness for approval. Investigators and patient advocates warned the requirement presents ethical challenges because it would require some participants to wait years for an effective, potentially life‑prolonging intervention and could render them ineligible later due to disease progression. uniQure has said the FDA could not rely solely on prior open‑label data and recommended the randomized design. The decision will materially affect uniQure’s development timeline, trial design, and the broader debate around control arms for invasive, one‑time gene therapies in rapidly progressive neurological diseases.