March 02, 2026- uniQure saw its shares fall roughly 35% after disclosing that the U.S. Food and Drug Administration (FDA) has maintained its position that Phase I/II data for its Huntington’s disease AAV gene therapy, AMT-130, are insufficient to support approval.
The feedback, detailed in minutes from a January Type A meeting, reinforces the FDA’s recommendation that the company conduct a new, prospective clinical trial. According to uniQure, the agency “strongly recommended” a randomized, double-blind, sham surgery-controlled study.
AMT-130 is an AAV5 gene therapy designed to silence the HTT gene by delivering an artificial microRNA to suppress production of the mutant huntingtin protein. The one-time AAV5 gene therapy is administered via burr holes in the skull, targeting the caudate nucleus and putamen through catheter-based infusion.
In September 2025, uniQure reported that 12 patients receiving a high dose of AMT-130 demonstrated a 75% slowing of disease progression at 36 months on the composite Unified Huntington’s Disease Rating Scale (cUHDRS), compared with a propensity score-matched external control cohort. The AAV5 gene therapy also showed a 60% slowing on Total Functional Capacity. Those results drove the company’s stock up more than 250% at the time.
However, regulators signaled late last year—and reiterated during the recent Type A meeting—that comparisons against external controls would not constitute primary evidence of effectiveness. CEO Matt Kapusta described the agency’s current stance as a “drastic change” from November 2024 guidance regarding a potential accelerated approval pathway for the AAV5 gene therapy.
Analysts noted that the requirement for a sham-controlled trial introduces meaningful development risk and cost, particularly given the invasive neurosurgical delivery of this AAV5 gene therapy. The situation gained additional attention after FDA Commissioner Marty Makary referenced a burr-hole–delivered therapy in a recent CNBC interview, stating that a product failed to show benefit at the end of its randomization period. Although not explicitly named, the remarks fueled speculation about AMT-130 and contributed to stock volatility.
uniQure stated that it remains committed to engaging with the FDA to establish a scientifically grounded and efficient development path for AMT-130. The company plans to request a Type B meeting in the second quarter to discuss potential Phase III study design approaches for the AAV5 gene therapy.
