UniQure's Huntington Disease Gene Therapy AMT-130 Snags FDA Breakthrough Therapy Designation

uniQure's AMT-130, an adeno-associated virus vector-based gene therapy currently being evaluated for the treatment of Huntington disease in 2 phase 1/2 clinical trials (NCT04120493 and NCT05243017), has been granted breakthrough therapy designation by the FDA.¹

Notably, AMT-130 has previously been granted regenerative medicine advanced therapy, orphan drug, and fast track designations by the agency. UniQure noted that as of April 2025, 45 patients have been treated with AMT-130.

“Receiving breakthrough therapy designation underscores both the urgent need for effective treatments for Huntington disease and the encouraging interim data demonstrating that AMT-130 has the potential to slow disease progression,” Walid Abi-Saab, MD, the chief medical officer at uniQure, said in a statement.¹ “It’s a powerful recognition of the promise of AMT-130 and the important progress we’ve made. We deeply value the FDA’s continued commitment to advancing innovative gene therapies for patients with critical unmet needs, and we look forward to working closely with the agency to bring AMT-130 to the Huntington disease patient community as quickly as possible.”

The designation was granted partially based on findings from the aforementioned trials, data from which were most recently reported in July 2024.^1,2 The interim data came from 39 patients enrolled in the ongoing United States (n = 26) phase 1/2 trial (NCT04120493) and European (n = 13) phase 1/2 trial (NCT05243017) who had up to 24 months of follow-up. In the July data update, uniQure compared data from patients who had received AMT-130 at that time to 154 propensity-weighted external control patients developed in collaboration with the Cure Huntington’s Disease Initiative (CHDI) from the TRACK-HD, TRACK-ON and PREDICT-HD natural history studies. The high-dose cohort had a mean change of –0.2 in composite Unified Huntington’s Disease Rating Scale (cUHDRS) compared with –1.0 in the external control (P = .007), representing an 80% slowing in disease progression. A –0.7 change was seen in the low-dose cohort, which constituted a statistically insignificant change in disease progression of 30% (P = .21). At 24 months posttreatment, a statistically significant reduction of 11% from baseline in neurofilament light chain (NfL) in the cerebrospinal fluid (CSF) was alsorecorded (P = .02).

“We are very pleased with these new data demonstrating a statistically significant, dose-dependent slowing of the progression of Huntington disease and lowering of NfL in the CSF at 24 months,” Abi-Saab said in a July 2024 statement.² “We believe this is the first clinical trial of any investigational medicine for Huntington’s disease to show evidence of a potential long-term clinical benefit and reduction of a key marker of neurodegeneration. Moreover, given the one-time administration of AMT-130, we are in a unique position to continue accumulating longer-term patient outcomes from the phase 1/2 studies to support the emerging therapeutic benefit. We look forward to holding an initial, multi-disciplinary RMAT meeting with the FDA later this year to discuss the potential for expedited clinical development of AMT-130.”

In December of last year, 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 biologics license application (BLA) for the gene therapy product can be sufficiently supported by data from the ongoing trials compared to external control natural history data. As such, an additional trial will not need to be carried out prior to submission of a potential BLA. An additional outcome of the meeting was the FDA’s determination 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 FDA Breakthrough Therapy Designation Granted to AMT-130 for the Treatment of Huntington’s Disease. News release. uniQure N.V. April 17, 2025. Accessed April 24, 2025. https://uniqure.gcs-web.com/node/12041/pdf
2. uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease. News release. uniQure. July 9, 2024. Accessed April 24, 2025. https://www.globenewswire.com/en/news-release/2024/07/09/2910220/0/en/uniQure-Announces-Positive-Interim-Data-Update-Demonstrating-Slowing-of-Disease-Progression-in-Phase-I-II-Trials-of-AMT-130-for-Huntington-s-Disease.html#
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 April 24, 2025. https://uniqure.gcs-web.com/node/11906/pdf