A senior FDA official publicly rejected uniQure’s characterization of agency actions and defended a request for a randomized, sham‑controlled trial of AMT‑130, the company’s intracranial gene therapy for Huntington’s disease. The agency said external control data submitted by uniQure are insufficient and reiterated a long‑standing policy favoring internal randomized data for heterogeneous, invasive neurologic interventions. uniQure earlier argued that a sham arm would pose unacceptable risks to patients; the FDA countered that the requested control would be brief and limited to scalp incisions and anesthesia rather than full invasive procedures. The exchange escalated after agency spokespeople publicly criticized the company’s data and prior communications. The dispute follows a history of high regulatory scrutiny for Huntington’s candidates after prior trial failures such as Roche/Ionis’ tominersen. Regulatory implications are immediate: the FDA’s stance increases trial burden for invasive CNS gene therapies and signals the agency will press for randomized confirmatory evidence even when sponsors propose natural history or external controls. For readers: a sham‑controlled trial refers to a randomized design in which control patients undergo procedural steps that mimic treatment to blind outcomes; regulators cite this when subjective endpoints or large placebo effects are plausible.