FDA Reverses on UniQure’s Huntington’s Disease Gene Therapy as Company Plans to Seek Accelerated Approval

Rare Daily Staff

The U.S. Food and Drug Administration in a reversal has agreed that mid-stage clinical data could support an accelerated approval filing for UniQuire’s experimental gene therapy AMT-130 in Huntington’s disease, positioning the company to submit an as application for marketing approval as early as the third quarter of 2026.

The agency had previously said it wanted an additional study before it would consider whether or not to approve the gene therapy.

The guidance follows a recent Type B meeting in which the FDA indicated that three-year data from the ongoing phase 1/2 program may serve as the primary basis for an accelerated approval submission. The agency also requested alignment on the design of a confirmatory study prior to filing, including the potential use of a concurrent standard-of-care control arm rather than a sham procedure. UniQure said it expects to finalize details of the confirmatory trial with the agency in the coming months.

UniQure CEO Matt Kapusta described the feedback as a key regulatory milestone, noting that the company believes the consistency and durability of clinical data generated to date support the therapy’s potential benefit. The FDA has granted AMT-130 Regenerative Medicine Advanced Therapy, Breakthrough Therapy, and Fast Track designations, underscoring the high unmet need in Huntington’s disease, where no approved treatments currently slow disease progression.

AMT-130 is an adeno-associated virus-based gene therapy designed to reduce production of the mutant huntingtin protein through a one-time neurosurgical administration directly into the striatum. The ongoing clinical program includes multiple dose-escalation cohorts across the U.S. and Europe, evaluating safety, tolerability, and exploratory efficacy in patients with early manifest disease. In the U.S. study, 26 patients were randomized to low-dose, high-dose, or sham procedure arms, with additional patients later crossing over to treatment. A parallel European open-label study and subsequent cohorts are exploring dosing strategies and the role of immunosuppression.

For the planned BLA, UniQure intends to compare treated patients from early cohorts against a propensity score-matched external control derived from the Enroll-HD natural history dataset, under a prespecified statistical analysis plan. Such external control strategies have become more common in rare disease development but remain subject to regulatory scrutiny, particularly in neurodegenerative indications.

Huntington’s disease is a rare, inherited disorder caused by a CAG repeat expansion in the huntingtin gene, leading to progressive motor dysfunction, cognitive decline, and psychiatric symptoms. Approximately 75,000 people across the U.S., Europe, and the U.K. are affected, with many more at risk of inheriting the condition.

If accepted, the application would mark one of the first gene therapies targeting Huntington’s disease to reach the regulatory review stage and could further test the FDA’s flexibility in applying accelerated approval pathways to neurodegenerative disorders with limited treatment options.

Photo: UniQure CEO Matt Kapusta