Positive Phase I/II study results for Huntington’s disease gene therapy
A pivotal study evaluating a gene therapy for Huntington’s disease successfully met its primary endpoint, showing a remarkable 75% slowing of disease progression at 36 months compared to an external control.
uniQure N.V. (MA, USA) has reported positive results from its Phase I/II study of AMT-130, a gene therapy for Huntington’s disease. The findings revealed that the treatment significantly slowed disease progression compared to untreated patients, providing new hope for those impacted by this debilitating neurodegenerative condition.
Huntington’s disease, a rare inherited neurodegenerative disorder, affects approximately 75,000 people across the US, EU and UK. Characterized by progressive physical and mental deterioration, the condition is caused by a mutation in the huntingtin gene, leading to the accumulation of abnormal protein in the brain. Despite understanding its genetic cause, there are currently no approved therapies to delay the onset or slow the progression of the disease.
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AMT-130, a gene therapy developed by uniQure to treat Huntington’s disease, is currently being evaluated in two multi-center, dose-escalating Phase I/II clinical studies to assess its safety, tolerability and efficacy. In its latest report, uniQure shared promising results from a pivotal study involving 29 patients, with 17 receiving a high dose and 12 receiving a low dose of AMT-130. Among these, 12 patients from each dose group completed 36 months of follow-up and were evaluated at 36 months.
The trial successfully met its primary endpoint with patients receiving the higher dose of AMT-130 demonstrating a 75% slowing of disease progression after 36 months, as measured by a standard Huntington’s disease rating scale. These patients experienced minimal decline compared to untreated matched patients. Additionally, the study achieved a key secondary endpoint, demonstrating that the therapy slowed the decline in patients’ ability to function independently by 60%.
Cognitive and motor tests, including assessments of thinking speed, reading ability and motor control, showed significant improvements in treated patients. Furthermore, the treatment demonstrated positive effects on a key biomarker of neurodegeneration, with patients showing a mean reduction from baseline in cerebrospinal neurofilament light protein (CSF NfL) of -8.2%. This is particularly significant as elevation in CSF NfL levels are strongly associated with greater clinical severity in Huntington’s disease. The therapy was generally well-tolerated at both dose levels and, as of 30 June 2025, no new serious drug-related adverse events have been reported since December 2022. These findings highlight the potential of AMT-130 to be a treatment option for Huntington’s disease.
“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease,” expressed Walid Abi-Saab, chief medical officer of uniQure. “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”
AMT-130 has been granted Breakthrough Therapy designation and Regenerative Medicine Advanced Therapy designation by the US Food and Drug Administration (FDA; MD, USA), demonstrating its potential to address the unmet needs of Huntington’s disease patients.
uniQure plans to discuss the data with the FDA later this year at a pre-Biologics License Application meeting, aiming to submit the application in early 2026.
“Today’s outcome reflects the tireless commitment of so many at uniQure, and I want to extend my deep gratitude to the team, as well as to the investigators, site personnel, patients, and families who made this possible,” continued Abi-Saab.
