A senior FDA official publicly defended the agency’s reviewers and reiterated that uniQure must conduct a randomized sham‑controlled study to support approval of AMT‑130, its intracranial gene therapy for Huntington’s disease. The FDA clarified the requested control would require patients to be anesthetized with scalp incisions rather than partial skull burr holes, disputing uniQure’s characterization of an ethically untenable placebo arm. UniQure had relied on pivotal Phase 1/2 data and external controls showing marked slowing of disease progression, but the agency in late 2025 said those data were no longer adequate as primary evidence for a BLA. The public back-and-forth raises timelines and trial-design stakes for AMT‑130 and underscores broader regulatory scrutiny of invasive gene therapies where effect sizes and trial heterogeneity complicate approval pathways.