uniQure's AMT-130 Shows Continued Slowing of Huntington's Disease at 48 Months, Though Primary Endpoint Misses Significance

uniQure has reported additional 36-month and 48-month data from its ongoing phase 1/2 studies of ifezuntirgene inilparvovec (AMT-130), an investigational one-time gene therapy for Huntington's disease, the company announced on September 29, 2026.¹ The analyses, with a data cutoff of June 30, 2026, compared treated patients with propensity score-matched external controls drawn from an updated ENROLL-HD natural history dataset.¹ The new results were not part of the Biologics License Application (BLA) uniQure submitted earlier this month.¹

What did the updated 36-month analysis show?

The 36-month timepoint is the regulatory anchor for the submitted BLA and the planned confirmatory study, according to uniQure.¹ The updated analysis added three high-dose patients who had reached 36 months since the company's September 2025 readout, bringing the high-dose group to 15.¹

In these 15 patients, the composite Unified Huntington's Disease Rating Scale (cUHDRS) showed 80% slowing of disease progression versus the external control (nominal p=0.005), with a mean change from baseline of −0.28 compared with −1.39 in controls.¹ Total Functional Capacity (TFC) showed 67% slowing (nominal p=0.011).¹ In the September 2025 analysis of 12 high-dose patients, uniQure had reported 75% slowing on cUHDRS (p=0.003) and 60% slowing on TFC (p=0.033) at 36 months.³

What happened at 48 months?

In 12 high-dose patients at 48 months, cUHDRS showed 44% slowing of disease progression, which did not reach statistical significance (p=0.144).¹ TFC showed 61% slowing (nominal p=0.008), with a mean change from baseline of −0.37 versus −0.94 in the external control.¹ High-dose patients also declined less than low-dose patients on both measures, which uniQure said is consistent with a dose-dependent treatment effect.¹

uniQure attributed the smaller cUHDRS effect partly to the external control. Missing data in the updated ENROLL-HD matched controls reached 53% at 48 months, and the company's analysis showed that patients who discontinued follow-up were progressing materially faster than those who remained.¹ In a post hoc sensitivity analysis using the prior ENROLL-HD control, the 48-month results showed 53.5% slowing on cUHDRS (nominal p=0.041) and 68.3% on TFC (nominal p=0.001).¹

"Total Functional Capacity tracks things that matter the most to patients and families – ability to work, perform household chores and handle daily self-care activities," said Victor Sung, MD, professor of neurology at the University of Alabama at Birmingham and director of the UAB Huntington's Disease Clinic.¹ TFC is the primary measure of uniQure's confirmatory study.¹

How does ifezuntirgene inilparvovec work?

Huntington's disease is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the huntingtin gene, which leads to production and aggregation of abnormal protein in the brain.¹ Ifezuntirgene inilparvovec uses an adeno-associated virus 5 (AAV5) vector to deliver a microRNA designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment.¹,⁴ Patients receive a single administration through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum.¹

In a 2021 article for BioPharm International®, Paul Larson, MD, then professor and vice-chair of neurological surgery at the University of California San Francisco, wrote that for therapies delivered to the brain, "the method of delivery is often relegated to an afterthought." Writing about CNS delivery generally rather than about ifezuntirgene inilparvovec, Larson noted that real-time intraoperative MRI-guided infusion "has enabled larger volumes of delivered therapeutics and tactics, such as varying infusion rates and adjusting cannula depth/position to maximize coverage."

What about safety?

uniQure said the therapy continues to be generally well tolerated at both doses, with the most common adverse events related to the administration procedure, all of which resolved.¹ As previously disclosed, five high-dose participants (17%) experienced a treatment-related serious adverse event related to central nervous system inflammation, all of which fully resolved.¹ Since the September 2025 readout, one low-dose patient died by suicide approximately five years after treatment, an event the study investigator assessed as unrelated to treatment.¹ uniQure noted that suicide occurs at substantially elevated rates in Huntington's disease.¹

What happens next?

uniQure submitted its BLA to the FDA on September 2, 2026, under the accelerated approval pathway and requested priority review.¹,² At a June 2026 Type B meeting, the FDA communicated that 36-month data from 12 high-dose patients would be acceptable as the primary basis for the submission.¹ The company plans to present the new data at a future scientific meeting.¹

References

1. uniQure. uniQure Announces Additional Data from Ongoing Phase I/II Studies of ifezuntirgene inilparvovec (AMT-130) in Huntington's Disease Showing Continued Slowing of Disease Progression. Press release. Published September 29, 2026. Accessed September 29, 2026.
2. uniQure. uniQure Announces Submission of Biologics License Application for Ifezuntirgene Inilparvovec (AMT-130) in Huntington's Disease. Press release. Published September 2, 2026. Accessed September 29, 2026.
3. uniQure. uniQure Announces Positive Topline Results from Pivotal Phase I/II Study of AMT-130 in Patients with Huntington's Disease. Press release. Published September 24, 2025. Accessed September 29, 2026.
4. Huntington Study Group. Meet the Compound: AMT-130. Published April 30, 2024. Accessed September 29, 2026.