uniQure receives FDA pushback on approval pathway for Huntington’s disease gene therapy

In a notice with implications for the broader Huntington’s disease development landscape, uniQure N.V. (NASDAQ: QURE) announced that it received final meeting minutes from the US FDA following a Type A meeting held on January 30, 2026, to discuss AMT-130, an investigational AAV5-based gene therapy for Huntington’s disease.

The agency stated that it cannot agree that data from the Phase I/II studies of AMT-130 Huntington’s disease program, compared against an external control arm, are sufficient to provide the primary evidence of effectiveness required to support a marketing application. The FDA strongly recommended that uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study before seeking approval.

FDA’s stated rationale and practical implications

The FDA’s position centered on the adequacy of evidence of effectiveness. The agency determined that data generated from the company’s Phase I/II clinical trials, when benchmarked against an external comparator rather than a concurrent randomized control group, did not meet the evidentiary standard required for a Biologics License Application. The FDA’s strong recommendation for a prospective, randomized, double-blind, sham surgery-controlled trial indicates that the agency views a concurrent control arm — including a sham surgical procedure — as necessary to account for potential placebo effects and confounding variables inherent in open-label neurosurgical studies.

For uniQure, a Phase III study of the design recommended by the FDA would require substantial additional time and capital. Enrollment of patients willing to undergo randomization to a sham neurosurgical procedure in a progressive, fatal neurodegenerative disease presents its own operational and ethical complexities. The timeline to a potential marketing application is now extended by several years at minimum.

Matt Kapusta, CEO of uniQure, stated that while the company did not reach alignment on a submission pathway based on Phase I/II data, the company believes the totality and durability of its data warrant continued dialogue regarding how the FDA’s stated commitment to regulatory flexibility may be applied. The company said it intends to continue engaging with the FDA regarding Phase III development considerations and plans to request a Type B meeting in the second quarter of 2026 to discuss potential study design approaches.

The AMT-130 gene therapy

Huntington’s disease is a progressive, hereditary neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. The disease leads to motor dysfunction, cognitive decline, and psychiatric disturbances, and is uniformly fatal.

AMT-130 is a one-time, adeno-associated virus serotype 5-based gene therapy that delivers an engineered microRNA designed to silence expression of the huntingtin gene through RNA interference. The therapy is administered directly to the striatum via MRI-guided stereotactic neurosurgery. By reducing levels of the toxic mutant huntingtin protein, AMT-130 aims to address the underlying genetic cause of Huntington’s disease rather than merely managing symptoms.

The only FDA-approved treatments for Huntington’s disease — tetrabenazine (Xenazine, approved 2008) and deutetrabenazine (Austedo, approved 2017) — are VMAT2 inhibitors that address chorea symptoms only. The AMT-130 clinical trial program therefore targets an area of profound unmet medical need.

The miRNA technology underlying AMT-130 originated in academic research on RNA interference approaches to huntingtin gene silencing. uniQure subsequently developed the AAV5-vectored construct internally using its proprietary adeno-associated virus platform.

CSL Behring completed its acquisition of uniQure in 2024, which transferred stewardship of the entire uniQure pipeline, including AMT-130, to CSL. The regulatory and development strategy for the program now falls under CSL’s broader organizational structure, though the company continues to operate under the uniQure name for this program.