Gene Therapy Slows Huntington Disease Progression in Phase 1/2 Trial
Patients with Huntington disease who received a high dose of the gene therapy AMT-130 experienced 75% less disease progression after 36 months compared with a propensity score-matched external cohort that did not receive the treatment, announced gene therapy developer uniQure.
The pivotal phase 1/2 trial included 17 patients treated with a high dose and 12 with a low dose of AMT-130. The analysis focused on 12 patients from each dose group who, as of June 30, 2025, had completed 36 months of follow up. Outcomes for each group were compared with patients in the Enroll-HD natural history study: 940 matched patients for the high-dose group and 626 matched patients for the low-dose group.
High-dose AMT-130 met the study’s prespecified primary endpoint of statistically significant slowing of disease progression, as measured by the composite Unified Huntington’s Disease Rating Scale, compared with controls at 36 months. Patients treated with AMT-130 had a mean change of -0.38 compared with -1.52 for external controls.
Patients who received high-dose AMT-130 also demonstrated 60% slowing of disease progression as measured by the Total Functional Capacity scale compared with external controls. The mean change was -0.36 with AMT-130 compared with -0.88 for external controls.
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High-dose AMT-130 was further associated with 88% slowing of disease progression on the Symbol Digit Modalities Test, 113% slowing of disease progression as measured by Stroop Word Reading Test, and 59% slowing of disease progression on the Total Motor Score compared with external controls.
Additionally, levels of cerebrospinal neurofilament light protein (NfL), a marker of neuronal damage in patients with Huntington disease, were 8.2% lower in patients 36 months after receiving AMT-130 compared with at the trial’s start. Without the therapy, NfL levels would have been expected to increase 20% to 30% over that time.
Trends in the low-dose AMT-130 group were variable, uniQure reported, suggesting a dose-dependent response to the gene therapy.
AMT-130 was generally well-tolerated, with a manageable safety profile.
“l am thrilled that this study of AMT-130 showed statistically significant effects on disease progression at 36 months,” said neurologist Sarah Tabrizi, MD, PhD, director of the Huntington disease center at University College London, London, England, and the trial’s lead scientific advisor. “These groundbreaking data are the most convincing evidence in the field to date and underscore the disease-modifying effect in Huntington disease, where an urgent need persists. For patients, AMT-130 has the potential to preserve daily function, keep them in work longer, and meaningfully slow disease progression.”
Results from the trial will be presented in mid-October at the HD Clinical Research Congress in Nashville, Tennessee. uniQure plans to request accelerated approval from the US Food and Drug Administration for AMT-130 early next year.
“My patients in the trial are stable over time in a way I’m not used to seeing in Huntington disease,” said neurologist Ed Wild, MD, principal investigator at the University of College London trial site, “and 1 of them is my only medically-retired Huntington disease patient who has been able to go back to work.”
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