FDA Accepts uniQure’s Huntington’s Disease Gene Therapy BLA for Priority Review

FDA has accepted uniQure’s Biologics License Application (BLA) for ifezuntirgene inilparvovec (AMT-130), a one-time gene therapy for Huntington’s disease, and granted it priority review under the accelerated approval pathway.¹ The target action date is May 1, 2027, and FDA said it is tentatively planning an advisory committee meeting to discuss the application.¹

“Backed by compelling data from our phase 1/2 studies, we believe ifezuntirgene inilparvovec has the potential to become the first disease modifying treatment for Huntington’s disease,” said Matt Kapusta, chief executive officer of uniQure.¹

How does AMT-130 work?

Huntington’s disease is a rare, inherited neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, leading to movement problems, behavioral changes, and cognitive decline.¹ About 75,000 people in the US, EU, and UK have the disease, and no approved therapy slows its progression.¹

AMT-130 uses uniQure’s miQURE gene-silencing platform to deliver a microRNA designed to silence the huntingtin gene and its toxic exon 1 protein fragment.¹ The therapy is administered once through MRI-guided, convection-enhanced stereotactic neurosurgery directly into the striatum, a brain region affected early in the disease.¹ It holds FDA Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), and Fast Track designations.¹

What data support the BLA?

The application is based on 36-month data from phase 1/2 studies compared with a propensity score-matched external control drawn from the Enroll-HD natural history database.¹ In September 2025, uniQure reported that high-dose AMT-130 slowed disease progression by 75% on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) at three years compared with the external control, meeting the study’s primary endpoint.² An updated three-year analysis of 15 high-dose patients later showed 80% slowing on cUHDRS and 67% slowing on Total Functional Capacity.³

Four-year data reported in September 2026 were less pronounced. In 12 high-dose patients, AMT-130 slowed cUHDRS decline by 44% vs an updated external control, a difference that was not statistically significant, and slowed decline on Total Functional Capacity by 61%.³ uniQure said that 53% of the updated control data were missing and that the effect was likely understated.³ The company’s shares fell about 40% after the update.³

How did the application reach FDA?

The filing follows a series of reversals in FDA’s position. After the three-year data, FDA questioned the study design, and in November 2025 said the data were not adequate as primary evidence for a BLA, before changing course again in the spring of 2026.⁴ uniQure submitted the BLA in September 2026.⁴ Former FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research director Vinay Prasad, who had made negative comments about the therapy, have since left the agency.⁴ Analysts at Stifel called the acceptance an “incrementally positive sign” for accelerated approval.⁴

Expedited designations increase interaction with FDA but do not lower the evidence bar. In a BioPharm International® Drug Digest video interview on expedited regulatory pathways for biologics, Steven Quay, MD, PhD, founder and chief executive officer of Atossa Therapeutics, cautioned against that assumption. “You don’t think that an expedited pathway that can get you an approval faster allows you to do less work,” Quay said.

What happens next?

As a condition of accelerated approval, uniQure plans a randomized confirmatory trial of about 200 patients, assigned 2:1 to AMT-130 or standard of care, with Total Functional Capacity at 36 months as the primary endpoint.¹ Screening is expected to begin in the US by the end of 2026.¹

“The confirmatory trial remains a key priority, with screening anticipated to begin by year end and the study is expected to be well underway by the time of potential approval,” Kapusta said.¹

References

1. uniQure announces FDA acceptance and priority review of the Biologics License Application for ifezuntirgene inilparvovec for the treatment of Huntington’s disease. News release. uniQure. November 2, 2026. Accessed November 2, 2026.
2. UniQure “exceeds expectations” in much-anticipated 3-year Huntington’s readout. BioSpace. September 24, 2025. Accessed November 2, 2026.
3. Bell J. UniQure Huntington’s four-year data. BioPharma Dive. September 29, 2026. Accessed November 2, 2026.
4. UniQure snags May Day decision date for Huntington’s gene therapy after arduous year. BioSpace. November 2, 2026. Accessed November 2, 2026.