Phase 1/2 Trial for uniQure's Huntington Disease Gene Therapy AMT-130 Hits Primary End Point

Findings from a phase 1/2 clinical trial evaluating uniQure's AMT-130, an adeno-associated virus vector-based gene therapy intended to treat Huntington disease, have shown that at 36 months posttreatment, high-dose AMT-130 was able to significantly slow disease progression by 75% in comparison to a propensity score-matched external control, as assessed by the Unified Huntington’s Disease Rating Scale (cUHDRS) (P = .003).¹

As such, the study has met its prespecified primary end point. Specifically, the change for the treated patients was -0.38 from baseline whereas the change for the external control was -1.52 from baseline.

The study also met a key secondary end point, as a statistically significant 60% slowing of disease progression in comparison to a propensity score-matched external control assessed at 36 months posttreatment via Total Functional Capacity (TFC) was also reported (P = .033). Specifically, the change for the treated patients was -0.36 from baseline whereas the change for the external control was -0.88 from baseline.

As of the June 30, 2025, data cut off, the treatment group used in the analysis above included 12 patients treated with a high dose of AMT-130 who had reached 36 months of follow-up. The propensity score-matched external control came from the Enroll-HD natural history study and included 940 patients for the high dose comparison.

In addition to the aforementioned results, the group of patients treated with high-dose AMT-130 who had reached 36 months of follow-up also showed an –8.2% decrease from baseline in cerebrospinal neurofilament light protein (CSF NfL). Furthermore, at 36 months the treated patients showed a mean change from baseline on the Symbol Digit Modalities Test of -0.44 compared to a –3.73 change for external control patients (88% slowing of disease progression, P = .057); a mean change from baseline on the Stroop Word Reading Test of 0.88 compared to a –6.98 change for external control patients (113% slowing of disease progression, nominal P = .002); and a mean change from baseline on Total Motor Score of 2.01 compared to a 4.88 change for external control patients (59% slowing of disease progression, P = .174).

“I am thrilled that this pivotal study of AMT-130 showed statistically significant effects on both cUHDRS and TFC at 36 months, supported by mean CSF NfL remaining below baseline,” Sarah Tabrizi, MD, FRCP, FRS, FMedSci, PhD, a professor of clinical neurology, director of the University College London Huntington’s Disease Center, and joint head of the department of neurodegenerative disease, said in a press release.¹ “I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists. These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.”

uniQure stated that the high-dose group for AMT-130 showed “consistently favorable” results with regard to functional, motor, and cognitive end points in comparison to “variable trends” in a low-dose group that included 12 patients who had reached 36 months of follow-up, thus indicating a dose-dependent response to the gene therapy. With regard to safety, the company characterized AMT-130 as “generally well-tolerated, with a manageable safety profile" at the low dose and the high dose. No new serious adverse events (AEs) related to the gene therapy have been reported between December 2022 and the data cut off. AEs related to the administration procedure, all of which resolved, constituted the most common AEs across treatment groups.

UniQure intends to submit a biologics license application (BLA) for AMT-130 to the FDA in the first quarter of next year. It also expects to hold a preBLA meeting with the agency before the end of 2025.

"We never in our wildest dreams would have expected a 75% slowing of clinical progression,” Tabrizi said in a separate statement reported by the BBC, noting that she was "overjoyed for the patients and families."²

In December of 2024, uniQure came into alignment with the FDA during a Type B meeting regarding the use of an accelerated approval pathway for AMT-130.³ Specifically, the agency agreed with the company that a BLA for the gene therapy product can be sufficiently supported by data from ongoing trials compared to external control natural history data, that cUHDRS may be used as an intermediate clinical end point for an accelerated approval, and that data demonstrating CSF NfL decreases can be used as supportive evidence for clinical benefit in this context.

REFERENCES
1. uniQure Announces Positive Topline Results from Pivotal Phase I/II Study of AMT-130 in Patients with Huntington’s Disease. News release. uniQure N.V. September 24, 2025. Accessed September 25, 2025. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii
2. Huntington's disease successfully treated for first time. News article. Gallagher, James, BBC. September 24, 2025. Accessed September 25, 2025. https://www.bbc.com/news/articles/cevz13xkxpro
3. uniQure Announces Alignment with FDA on Key Elements of Accelerated Approval Pathway for AMT-130 in Huntington’s Disease. News release. uniQure N.V. December 10, 2024. Accessed September 25, 2025. https://uniqure.gcs-web.com/node/11906/pdf