FDA informed uniQure it will not accept data from the company's Phase I/II studies as the primary basis for a marketing application for AMT-130, its investigational gene therapy for Huntington's disease.

The decision deals a significant blow to the biotech's hopes of an accelerated path to approval.

What did the FDA decide?

Following a Type A meeting held back on January 30, the agency issued final meeting minutes formally rejecting the external control approach uniQure had pursued, and strongly recommended the company conduct a prospective, randomized, double-blind, sham surgery-controlled study instead.

Following the decision, an anonymous FDA official in a call with media on Thursday March 5, then called uniQure’s treatment a “failed product,” along with reinforcing the agency’s decision to request an additional sham-controlled trial.²

“We asked uniQure to take their product and randomize patients to getting the treatment the way they give the treatment, which requires a skin incision, a hole in the skull and an intracranial injection of the product, versus a control arm, where all they do is anesthetize the patient and put one to three nicks in the scalp,” the unnamed senior FDA official said. “We did not ask them to compare against a partial sham burr hole.”

Why is the FDA demanding a sham-controlled trial?

The FDA's position reflects a long-standing agency policy for Huntington's candidates, rooted in the disease's complexity.² The agency has argued a placebo-controlled study is necessary because Huntington's is heterogeneous and patients are susceptible to a placebo effect, particularly given the subjective nature of its endpoints.¹

"We only ask for randomized data when a condition is heterogeneous, when the will to believe is strong, when the therapy is invasive or potentially harmful, when the effect size is difficult to detect and when the possibility you are fooling yourself is high," the FDA official said.

What is uniQure's argument against the FDA's position?

uniQure has pushed back on the decision, arguing the agency shifted its requirements after previously agreeing in writing that external control data could form the primary basis for an approval submission.¹ The FDA has flatly denied that account.

"FDA, as a general rule, never makes such assurances," the official said. "FDA will always say, 'Well, we have to see the data when we get it.'"

What does the trial data actually show?

At the heart of the dispute is uniQure's Phase I/II data showing AMT-130 slowed disease progression by 75% compared to patients drawn from a natural history database.³ The FDA does not dispute the figure itself, but questions whether those external patients represent a valid comparator, arguing they were never subject to a placebo effect because they never believed they had received treatment.²

What contradiction has the FDA flagged in uniQure's data?

The agency pointed to what it sees as a contradictory signal within uniQure's own dataset. Sham-controlled data from a small cohort of U.S. patients showed no treatment effect at 12 months, a finding the FDA said undermines the reliability of the external control comparison that did show benefit at the same timepoint.²

"If both of those statements are true, why do we see a benefit at one year in the external controlled data, but not in the randomized data?" the official asked.

What happens next?

uniQure plans to request a Type B meeting in the second quarter of 2026 to discuss potential study design approaches, signaling it has not abandoned efforts to find a viable path forward.¹

"We remain committed to engaging with the FDA to determine a clear, scientifically grounded, and efficient path forward for AMT-130," said Matt Kapusta, chief executive officer of uniQure. "We are deeply grateful for the resilience and support of the Huntington's disease community and remain committed to standing with patients and their families as we advance this potentially transformative therapy."

Sources

1. uniQure Provides Regulatory Update on AMT-130 for Huntington’s Disease. uniQure. March 2, 2026. https://www.uniqure.com/investors-media/press-releases
2. uniQure Announces 2025 Financial Results and Provides Recent Company Updates. uniQure. March 2, 2026. https://www.uniqure.com/investors-media/press-releases
3. FDA official calls UniQure's Huntington's disease treatment a failure. Reuters. March 5, 2026. https://www.reuters.com/business/healthcare-pharmaceuticals/sr-fda-official-calls-uniqures-huntingtons-disease-treatment-failure-2026-03-05/