FDA Allows AMT-130 Huntington Disease Data to Support Planned BLA Submission Under Accelerated Approval Pathway

The FDA has indicated that 3-year data from the phase 1/2 clinical program of AMT-130, an investigational gene therapy for Huntington disease (HD), may serve as the primary basis for a planned Biologics License Application (BLA) submission seeking accelerated approval. According to developer uniQure, the company expects to submit the application in the third quarter of 2026.¹

The regulatory update follows a recent Type B meeting between uniQure and the FDA, during which the agency requested additional alignment on the design of a confirmatory study that would follow a potential accelerated approval. According to the company, the FDA indicated that the confirmatory study may evaluate AMT-130 against standard-of-care therapy rather than requiring a sham procedure.

"Today's announcement reflects the outcome we have worked toward throughout our continued regulatory engagement with FDA, and we are deeply grateful for FDA's genuine commitment to addressing the unmet need of Americans living with Huntington's disease," Matt Kapusta, chief executive officer at uniQure, said in a statement.¹ "The FDA has agreed that our current clinical data can support a near-term BLA submission and has committed to work expeditiously with us to align on the design of the required confirmatory study."¹

The planned BLA submission will rely on 3-year analyses from ongoing phase 1/2 studies evaluating AMT-130 in adults with early manifest HD. As previously reported by NeurologyLive®, the US phase 1/2 study randomized 26 participants to receive low-dose AMT-130 (n = 6), high-dose AMT-130 (n = 10), or a sham surgical procedure (n = 10). Treated participants received a single administration of the gene therapy and entered long-term follow-up after completing a blinded 12-month core study period.²

At the 3-year analysis, the high-dose cohort met the study's primary end point, demonstrating a statistically significant slowing of disease progression compared with a propensity score–matched external control derived from the Enroll-HD natural history database. Using a June 30, 2025, data cutoff, investigators reported a 75% slowing of disease progression on the comprehensive Unified Huntington's Disease Rating Scale (cUHDRS), with a mean change of –0.38 in the high-dose AMT-130 group compared with –1.52 among matched external controls (P = .003). That analysis included 12 patients from both the high- and low-dose treatment cohorts and external control populations of 940 and 626 patients, respectively.²

Additional participants were evaluated through a European open-label phase 1b/2 study, which enrolled 13 individuals with early manifest HD. Subsequent cohorts were designed to further explore dosing approaches, immunosuppression strategies, and treatment in patients with lower striatal volumes compared with earlier participants. Across the clinical program, investigators have assessed safety, tolerability, biomarker changes, and exploratory measures of clinical efficacy.^1,2

As part of the potential regulatory package, data from cohorts 1 and 2 of the phase 1/2 program are allowed to be compared with a propensity score-matched external control derived from the Enroll-HD natural history database under a prespecified statistical analysis plan.¹ External controls may provide important context in rare disease studies where traditional trial designs can be difficult, although differences between treated populations and external comparator groups require careful interpretation.

The lack of approved disease-modifying therapies has fueled interest in huntingtin-lowering approaches designed to target the underlying biology of HD. However, the field has faced several development challenges in recent years, highlighting the difficulty of translating biologic effects into meaningful clinical benefit for patients.³

AMT-130 has received several FDA designations intended to facilitate development of therapies addressing serious conditions, including Regenerative Medicine Advanced Therapy (RMAT), Breakthrough Therapy, and Fast Track designations.¹ RMAT designation is available for regenerative medicine therapies with preliminary clinical evidence suggesting potential to address unmet medical needs.

Current treatment approaches for HD remain focused on symptom management, including therapies for chorea and associated psychiatric or behavioral manifestations. Although these treatments may improve specific aspects of disease burden, no approved therapy has been shown to slow or halt disease progression.²

The potential accelerated approval pathway would require confirmatory evidence to verify clinical benefit following authorization. Details regarding the design, comparator, and endpoints of the confirmatory study remain under discussion between uniQure and the FDA.¹

Because AMT-130 remains investigational, questions remain regarding the durability of any potential clinical effect, long-term safety of intracranial gene therapy delivery, and the relationship between biomarker changes and meaningful clinical outcomes. Future data from ongoing follow-up and confirmatory evaluation will help define the role of gene therapy approaches in Huntington disease management.

REFERENCES
1. uniQure Announces Plan for BLA Submission for AMT-130 in Huntington’s Disease. uniQure. News Release. June 17, 2026. Accessed June 17, 2026. https://www.uniqure.com/investors-media/press-releases
2. UniQure announces positive topline results from pivotal phase I/II study of AMT-130 in patients with Huntington’s disease. News release. UniQure. 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
3. Tabrizi, S.J., Flower, M.D., Ross, C.A. et al. Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol 16, 529–546 (2020). https://doi.org/10.1038/s41582-020-0389-4