uniQure Submits BLA and MAA for AMT-130 Gene Therapy in Huntington's Disease

uniQure submitted a Biologics License Application (BLA) to the FDA seeking accelerated approval of ifezuntirgene inilparvovec (AMT-130), an investigational gene therapy for Huntington's disease, and simultaneously submitted a Marketing Authorisation Application to the UK's Medicines and Healthcare products Regulatory Agency (MHRA) for the same therapy.¹ The company has requested priority review for the BLA, which, if granted, would shorten the FDA's review cycle to six months following the agency's 60-day filing review period.¹ Both submissions are supported by the previously announced three-year data analysis from the ongoing phase 1/2 clinical study, compared against a propensity score-matched external control derived from the Enroll-HD natural history database.¹ uniQure intends to present a four-year data analysis from the same studies before the end of the current quarter.¹

Matt Kapusta, chief executive officer at uniQure, said, "The submission of licensing applications for ifezuntirgene inilparvovec represents an important milestone for the Huntington's disease community. We are grateful to the FDA for its leadership in advancing regulatory science to meet the urgency of this disease, and to the MHRA for its commitment to advancing rare disease treatments in the U.K. We look forward to working with both agencies as these applications progress."¹

What does the three-year data show?

In the high-dose cohort, patients treated with AMT-130 demonstrated a statistically significant 75% slowing of disease progression on the composite Unified Huntington's Disease Rating Scale (cUHDRS) compared with the external control (p=0.003), with mean cUHDRS decline of –0.38 in treated patients versus –1.52 in controls, according to data presented at the 2026 American Academy of Neurology Annual Meeting.² Investigators also reported reductions in cerebrospinal fluid neurofilament light chain, a biomarker of neurodegeneration, with no new long-term safety concerns emerging during follow-up.² This three-year dataset has been presented at scientific meetings and reported in topline form by the company, but has not yet appeared in a peer-reviewed journal publication — uniQure has said it intends to publish the full dataset in a high-impact venue.³

How is AMT-130 delivered?

AMT-130 uses uniQure's proprietary miQURE gene-silencing platform, incorporating a microRNA designed to silence the huntingtin gene and its potentially toxic exon 1 protein fragment.¹ Unlike AAV gene therapies delivered systemically or via intrathecal injection, AMT-130 is administered through targeted, MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen).¹ BioPharm International has previously reported that interventional MRI-guided delivery gives surgeons a significantly higher degree of confidence that a cannula is following a safe trajectory to deep brain structures, where safe corridors can be as narrow as two to three millimeters.

A single administration is intended to provide durable, long-term silencing of the disease-causing gene. AAV vectors are non-pathogenic to humans and have low immunogenicity, and "can mediate long-term expression of the therapeutic gene, which is an important factor when treating chronic conditions that require sustained gene expression," according to Emmanuelle Cameau, strategic technology partnership leader, Genomic Medicine, at Cytiva.⁴ That durability premise underlies AMT-130's one-time-treatment design.

A recent peer-reviewed review of AAV-mediated gene therapy approaches specifically for Huntington's disease similarly notes that AAV vectors' non-pathogenic profile and capacity for sustained transgene expression have made them the most extensively employed and clinically validated platform for in vivo gene therapy, though the authors note AAV's potential for Huntington's disease specifically has remained comparatively underexplored relative to other rare genetic diseases.⁵

Why does this matter for Huntington's disease patients?

Huntington's disease is a rare, inherited neurodegenerative disorder affecting an estimated 75,000 people across the US, EU, and UK combined, with hundreds of thousands more at risk of inheriting the disease.¹ Despite a clear genetic cause, there are currently no approved therapies that delay onset or slow disease progression.¹ If approved, AMT-130 would be the first disease-modifying treatment for the condition; it is the first investigational Huntington's disease therapy to receive both Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA, and it also holds Fast Track designation.¹

What happens next?

The regulatory path here has not been straightforward: the FDA reversed its position multiple times over the past year on whether the existing phase 1/2 dataset was sufficient to support a BLA, before ultimately agreeing in June 2026 that the three-year analysis could serve as primary evidence.⁶ The FDA and MHRA will now conduct their respective filing reviews; if the FDA accepts the BLA for priority review, a decision could come within approximately eight months.

References

1. uniQure N.V. uniQure Announces Submission of Biologics License Application for Ifezuntirgene Inilparvovec (AMT-130) in Huntington's Disease. Press release. Published September 2, 2026. Accessed September 3, 2026.
2. Sung V. Understanding the 3-Year Findings Behind AMT-130 in Huntington Disease. Presented at: 2026 American Academy of Neurology Annual Meeting; Chicago, IL. Reported by NeurologyLive.
3. Gene Therapy for Huntington's Disease Faces New Regulatory Hurdle. Neurology Today. Published April 2, 2026. Accessed September 3, 2026.
4. Comparing Viral Vectors for Gene Therapy Delivery. BioPharm International. Published August 8, 2024. Accessed September 3, 2026.
5. Moeini Gavgani P, García-Domínguez M. Revolutionizing Huntington's Disease Treatment: Breakthroughs in AAV-Mediated Gene Therapy. Cells. 2025;14(19):1514. doi:10.3390/cells14191514
6. uniQure N.V. uniQure Announces Plan for BLA Submission for AMT-130 in Huntington's Disease. Press release. Published June 17, 2026. Accessed September 3, 206