FDA backtracks on Huntington’s disease gene therapy
Regulatory uncertainty for Huntington’s disease gene therapy.
During a recent pre-Biologics License Application (BLA) meeting, the US Food and Drug Administration (FDA; MD, USA) delivered unexpected feedback to uniQure (MA, USA) regarding its investigational gene therapy AMT-130 for Huntington’s disease. The agency indicated that it no longer agrees that Phase I/II data with external control comparison is adequate for BLA submission.
“We are surprised by the FDA’s feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing Phase I/II studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the Accelerated Approval pathway,” said Matt Kapusta, CEO at uniQure. “This news is unexpected, and we are truly disappointed for people living with [Huntington’s Disease], 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 U.S.”
Prior to this regulatory setback, AMT-130 was granted Breakthrough Therapy designation based upon data from the Phase I/II studies compared to external controls in April 2025 and Regenerative Medicines Advanced Therapy (RMAT) designation in May 2024.
On 24 September 2025, uniQure also released positive topline results from its Phase I/II study of AMT-130, demonstrating a 75% slowing of disease progression over 3 years compared to external controls at 36 months, meeting its prespecified primary endpoint with statistical significance (p=0.003).
Originally, uniQure planned to submit a BLA for AMT-130 in Q1 2026; however, following this regulatory discussion the timeline is now unclear. The company expects to receive final meeting minutes within 30 days and plans urgent interactions with the FDA to ensure the timely accelerated approval of AMT-130. In addition to ongoing partnership with the FDA, uniQure is planning parallel discussions with European Union and UK regulatory authorities.
About AMT-130
AMT-130 is a first-in-class, one-time gene therapy for Huntington’s disease, administered directly to the brain through a single neurosurgical procedure. The therapy is designed to silence the huntingtin gene and reduce production of the mutant protein (mHTT) that causes Huntington’s disease by utilizing AAV vectors to deliver micro-RNAs directly to the brain.