Gene Therapy AMT-130 Meets Endpoints in Huntington Study, FDA Submission to Follow

Data from the phase 1/2 program (NCT0543017, NCT04120493) of uniQure’s investigational gene therapy AMT-130 showed that the high dosed cohort met its primary end point, leading to statistically significant slowing of disease progression in patients with Huntington disease (HD) when compared with an external control. Based on these findings, the company is expected to submit a biologics license application (BLA) in the first quarter of 2026, positioning AMT-130 as a potential breakthrough treatment for the HD community.¹

The analysis featured 12 patients in both the high- and low-dose AMT-130 groups who had 36-month outcomes compared with to a propensity score-matched external control drawn from the Enroll-HD natural history data set (n = 940 for high dose; n = 626 for low dose). Overall, at the conclusion of the core study, investigators observed a 75% statistically significant slowing of disease progression, as measured by the comprehensive Unified Huntington’s Disease Rating Scale (cUHDRS).

Using a cutoff date of June 30, 2025, the decrease in disease progression resulted in a P value of 0.003, ultimately meeting the primary end point. The trial, which had protocol aligned with the FDA, revealed a mean cUHDRS change of –0.38 for those on AMT-130 vs changes of –1.52 for patients in the propensity score-matched external control.

"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, professor of neurology and director of the University College London Huntington’s Disease Center, said in a statement.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."

In December 2024, uniQure and the FDA aligned to discuss the pathway for AMT-130, which is expected to be submitted under the accelerated approval pathway. During their discussions, the agency concurred that data from the phase 1/2 program, which includes a U.S.-based and European-based trial utilizing the aforementioned Enroll-HD natural history external control as a comparator, could serve as the primary basis for a BLA submission. Ultimately, the parties’ decision would eliminate the requirement for an additional presubmission study.

UniQure and the FDA also aligned that the cUHDRS could be utilized as an intermediate clinical end point, with reductions in neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) to provide supportive evidence of therapeutic efficacy for the accelerated approval submission. In the latest data update, results showed a mean –8.2% reduction in CSF NfL from baseline, further upholding the drug’s potential as a treatment for HD.

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AMT-130 also met its secondary end point, demonstrating mean change of –0.36 points in total functional capacity (TFC), otherwise a 60% difference in comparison with propensity score-matched external controls (–0.88). Favorable trends were observed across motor and cognitive endpoints, including an 88% slowing on Symbol Digit Modalities Test (SDMT; P = 0.057; mean change, –0.44 vs –3.73), a 113% slowing on Swoop Word Reading Test (SWRT; P = 0.0021; mean change, 0.88 vs –6.98), and a 59% slowing on Total Motor Score (P = 0.1741; mean change, 2.01 vs 4.88) compared with external controls.

According to the company, the AMT-130 high dose continued to perform well against other external comparison datasets like TRACK-HD and PREDICT-HD. In addition, the gene therapy was reported as well-tolerated, with no serious adverse events (AEs) observed since December 2022. Both doses were considered safe, with common AEs attributed to the administration procedure, which were thus resolved.

The FDA has already granted breakthrough therapy designation and regenerative medicine advanced therapy (RMAT) designation to AMT-130 as a potential treatment for HD. To date, there are no FDA-approved disease-modifying or gene therapy medications available for patients with HD.

"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," Walid Abi-Saab, MD, chief medical officer at uniQure, said in a statement. "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. We are eager to discuss the data with the FDA at our pre-BLA meeting expected later this year, with the goal of submitting a BLA in the first quarter of 2026."

REFERENCES
1. uniQure Announces Positive Topline Results from Pivotal Phase I/II Study of AMT-130 in Patients with Huntington’s Disease. News release. September 24, 2025. Accessed September 24, 2025. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii
2. uniQure Announces Alignment with FDA on Key Elements of Accelerated Approval Pathway for AMT-130 in Huntington’s Disease. News Release. Published December 10, 2024. Accessed September 24, 2025. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-alignment-fda-key-elements-accelerated