LEXINGTON, Mass. — The U.S. Food and Drug Administration has accepted uniQure's application for its Huntington's disease gene therapy under priority review, putting the first potential disease-modifying treatment for the devastating inherited brain disorder on a path to a decision by 1 May 2027.
The agency accepted the Biologics License Application for ifezuntirgene inilparvovec, also known as AMT-130, under the accelerated approval pathway, uniQure announced on 2 November 2026. The FDA said it tentatively plans to discuss the application at an advisory committee meeting, though no date has been set.
Huntington's disease is a rare, inherited neurodegenerative disorder that causes involuntary movements known as chorea, behavioural changes and cognitive decline, leading to progressive physical and mental deterioration. About 75,000 people in the United States, the European Union and the United Kingdom have the disease, with hundreds of thousands more at risk of inheriting it, according to uniQure. There are currently no approved therapies that delay its onset or slow its progression — only treatments that manage symptoms.
Illustration: A stylised human brain with glowing DNA strands, representing gene therapy for Huntington's disease. This is an illustration, not a photograph of a real treatment.
What Happened
UniQure said the FDA granted priority review to the application, which shortens the agency's target review period, and set a Prescription Drug User Fee Act (PDUFA) target action date of 1 May 2027. The company said it has aligned with the FDA on key elements of a confirmatory trial: about 200 patients randomised two-to-one to receive the gene therapy or standard care, with total functional capacity as the primary endpoint at 36 months. Patient screening for that trial is expected to begin by the end of 2026, so the study should be well under way by the time of a potential approval.
“The FDA's acceptance of our BLA for review marks an important milestone for the Huntington's disease community, which has waited generations for a treatment that changes the course of this devastating disease,” uniQure chief executive Matt Kapusta said in the company's announcement. “Backed by compelling data from our Phase I/II studies, we believe ifezuntirgene inilparvovec has the potential to become the first disease modifying treatment for Huntington's disease.”
The therapy uses uniQure's miQURE platform: a microRNA designed to silence the huntingtin gene and the potentially toxic exon 1 protein fragment that drives the disease. Patients receive a single administration through targeted, MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum — the caudate and putamen regions of the brain.
“For uniQure, approval would be a defining milestone. It would validate our years of commitment to the Huntington's disease community and mark our transition to bringing a one-time treatment to patients who have waited decades for meaningful progress,” the company said, as reported by Fierce Biotech.
Background
Huntington's is an autosomal dominant condition caused by a CAG repeat expansion in the first exon of the huntingtin gene, which leads to the production and aggregation of abnormal protein in the brain. A child of an affected parent has a 50 per cent chance of inheriting the faulty gene, and those who inherit it will develop the disease if they live long enough.
The road to this filing has been turbulent. In 2022, dosing was paused for two groups in an open-label European phase 1/2 trial after a safety monitoring board recommended the pause when three patients were hospitalised with various symptoms; the pause was lifted in November 2022. In September 2025, uniQure reported that patients who received the higher dose showed a statistically significant 75 per cent slowing of disease progression at the 36-month mark. Shortly afterwards, the FDA no longer agreed that the study data were enough to support an approval filing, before changing its mind again in June 2026 and giving the company the go-ahead to file for accelerated approval.
Most recently, a 48-month analysis showed a 44 per cent slowing of disease progression on the composite Unified Huntington's Disease Rating Scale, falling short of statistical significance — a result that sent the company's shares down 41 per cent, according to Fierce Biotech. The FDA submission itself, a uniQure spokesperson told Fierce Biotech, was based on the 36-month analysis publicly shared in September 2025.
The phase 1/2 programme has dosed 51 patients in total. The U.S. randomised study enrolled 26 patients — six on a low dose, ten on a high dose and ten on a sham procedure, with four control patients crossing over to treatment after about 12 months. The European open-label study enrolled 13 patients, a third cohort of 12 explored both doses with immunosuppression, and a fourth cohort of six U.S. patients is evaluating the high dose in patients with lower striatal volumes.
Illustration: A patient and family talking with a doctor about a one-time brain gene therapy. This is an illustration, not a photograph of real patients.
Why It Matters
If approved, ifezuntirgene inilparvovec would be the world's first disease-modifying treatment for Huntington's disease — a field where decades of research have produced symptom management but nothing that changes the disease's course. For families who watch the disease unfold across generations, even a slowing of progression would be a landmark.
The decision also matters for the wider gene therapy field. Huntington's is a genetically clear-cut disease — a single faulty gene with a known toxic protein — which makes it a strong test case for gene-silencing approaches. A successful approval could validate the platform for other neurodegenerative conditions, while a rejection would raise fresh questions about how much evidence regulators require from small, early-stage trials in rare diseases.
The accelerated approval pathway itself is under scrutiny. It allows approval based on an intermediate endpoint reasonably likely to predict clinical benefit, with a confirmatory trial required afterwards. That trade-off — earlier access against residual uncertainty — is exactly what the planned 200-patient confirmatory trial is designed to resolve, and the FDA's tentative advisory committee meeting suggests the agency wants outside experts to weigh in publicly.
For uniQure, the stakes are existential as well as scientific. The company already has a historic gene therapy approval for haemophilia B, but Huntington's would mark its transition, in its own words, to bringing a one-time treatment to a community that has waited decades. The 41 per cent share-price fall after the 48-month data shows how finely investors are balancing hope against statistical rigour.
What Happens Next
Three milestones will shape the coming months. First, the FDA will set a date for its advisory committee meeting, where independent experts will publicly discuss the application — a session that often signals how the agency is leaning. Second, uniQure plans to begin screening patients for the confirmatory trial by the end of 2026, with the study expected to be well under way by the PDUFA date. Third, the PDUFA target action date itself falls on 1 May 2027, when the FDA is expected to approve, reject or request more information.
Even an approval would not end the story. Under accelerated approval, uniQure must complete the confirmatory trial to verify clinical benefit, and the FDA could withdraw approval if that benefit is not confirmed. Access questions would follow too: a one-time neurosurgical brain treatment requires specialised centres, MRI-guided delivery and follow-up, raising questions about cost, capacity and which patients are treated first.
Patients and families, meanwhile, are advised to discuss any treatment decisions with their own clinicians. This article is general information only and is not medical advice; the therapy described here is investigational and has not been approved.
Illustration: A health agency building with review documents, a microscope and a decision calendar. This is an illustration, not a photograph of a real regulatory office.
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FAQ
What is ifezuntirgene inilparvovec (AMT-130)?
It is uniQure's investigational one-time gene therapy for Huntington's disease, which uses a microRNA designed to silence the huntingtin gene. It is delivered once, directly into the striatum of the brain, through MRI-guided neurosurgery.
What did the FDA decide on 2 November 2026?
The FDA accepted uniQure's Biologics License Application for review under the accelerated approval pathway, granted priority review, set a PDUFA target action date of 1 May 2027, and said it tentatively plans to hold an advisory committee meeting.
Does priority review mean the therapy is approved?
No. Acceptance for review and priority review only mean the FDA will evaluate the application on a shortened timetable. Approval, rejection or a request for more information remains to be decided by 1 May 2027.
What evidence supports the application?
The submission is based on the 36-month analysis of the phase 1/2 programme, shared in September 2025, in which higher-dose patients showed a statistically significant 75 per cent slowing of disease progression. A later 48-month analysis showed 44 per cent slowing, falling short of statistical significance.
What is Huntington's disease?
It is a rare, inherited neurodegenerative disorder caused by a faulty huntingtin gene, leading to involuntary movements, behavioural changes and cognitive decline. About 75,000 people in the US, EU and UK have it, and there is currently no approved treatment that slows its progression.
Sources
- uniQure N.V., press release via GlobeNewswire, “uniQure Announces FDA Acceptance and Priority Review of the Biologics License Application for Ifezuntirgene Inilparvovec for the Treatment of Huntington's Disease,” 2 November 2026.
- Fierce Biotech, “FDA grants uniQure priority review of its Huntington's drug,” 2 November 2026.
- uniQure Phase I/II clinical programme details, ClinicalTrials.gov NCT05243017 and NCT04120493, as cited in the company's 2 November 2026 announcement.
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