PreBLA Meeting With FDA Sinks uniQure’s Hopes for Approval of Huntington Disease Gene Therapy AMT-130 Based Primarily on Phase 1/2 Data

uniQure has announced that based on feedback it received during a recent prebiologics license application (preBLA) meeting with the FDA, it no longer believes that the agency will find data from phase 1/2 studies compared to an external control sufficient to support a BLA for AMT-130, an adeno-associated virus vector-based gene therapy intended to treat Huntington disease (HD).¹

uniQure pointed out that this stands in contrast to its previous communications with the FDA in several Type B meetings, in which the agency had previously indicated alignment with uniQure’s plan to submit a BLA based primarily on phase 1/2 data. Although, the company noted that final minutes of the preBLA meeting have not yet become available, but are expected to be received within 30 days of the meeting. uniQure stated its intent to continue interaction with the FDA with the intent of finding a path for a “timely accelerated approval” of the gene therapy product.¹ At the moment, however, the company stated that its expected timeframe for a BLA submission is unclear. Alongside its ongoing interactions with the FDA, uniQure plans to advance discussions with regulatory bodies for countries other than the United States.

“We are surprised by the FDA’s feedback at the recent preBLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing phase 1/2 studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the accelerated approval pathway,” Matt Kapusta, MBA, the chief executive officer of uniQure, said in a statement.¹ “This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease. We strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the US.”

In December 2024, uniQure announced that it had come into agreement with the FDA regarding the use of an accelerated approval pathway for AMT-130 based on data from 2 phase 1/2 clinical trials (NCT04120493 and NCT05243017) compared to external control natural history data, negating the need to launch another trial before submission.² Furthermore, it was determined that for an accelerated approval the composite Unified Huntington’s Disease Rating Scale (cUHDRS) may constitute an intermediate clinical end point and that supportive evidence of clinical benefit can come in the form of data showing cerebrospinal fluid (CSF) neurofilament light chain (NfL) decreases.

In September 2025, uniQure announced that data from one of the phase 1/2 trials had shown that at 36 months post treatment, high-dose AMT-130 was able to significantly slow disease progression by 75% in comparison with a propensity score-matched external control, as assessed by cUHDRS (P = .003), and that it had thus met its primary end point.³ 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 with a propensity score-matched external control assessed at 36 months post treatment via Total Functional Capacity (TFC) was also reported (P = .033).

The study also met a key secondary end point, as a statistically significant 60% slowing of disease progression in comparison with a propensity score-matched external control assessed at 36 months post treatment via Total Functional Capacity (TFC) was also reported (P = .033).

“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, PhD, FRCP, FRS, FMedSci, a professor of clinical neurology, director of the University College London Huntington’s Disease Centre, and joint head of the Department of Neurodegenerative Disease, said in a press release at the time.³ “I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in HD, 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.”

REFERENCES
1. uniQure provides regulatory update on AMT-130 for Huntington’s disease. News release. UniQure N.V. November 3, 2025. Accessed November 3, 2025. https://www.uniqure.com/investors-media/press-releases
2. 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 November 3, 2025. https://www.uniqure.com/investors-media/press-releases
3. 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 November 3, 2025. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-positive-topline-results-pivotal-phase-iii