AAV Gene Therapy AMT-130 Faces Regulatory Hurdle

December 04, 2025- PHILADELPHIA — Investor confidence in uniQure has sharply declined after the company released final minutes from its pre-Biologics License Application (BLA) meeting with the FDA, confirming earlier guidance that data from its Phase I/II studies of the AAV gene therapy, AMT-130, are “currently unlikely to provide the primary evidence to support a BLA submission.”

The final feedback from the FDA places the regulatory road to market for the Huntington’s disease AAV gene therapy on a longer and more complex path than uniQure and analysts had anticipated.

FDA Reversal Jolts AAV Gene Therapy Timeline

The final minutes echo initial feedback shared on November 3, which had already caused uniQure’s stock to plummet from over $67 to $26. The stock price continued its decline, falling to just under $23 following the latest announcement.

The FDA’s position represents a seeming reversal of prior guidance, as uniQure had previously aligned with the agency on the design and statistical analyses of its Phase I/II trials. The trial design relied on comparing the efficacy of the AAV gene therapy, AMT-130, against a natural history external control to demonstrate its benefit in slowing disease progression.

• Prior Optimism: Just weeks earlier, on September 24, uniQure had reported highly positive three-year data from the trial, showing the AAV gene therapy slowed Huntington’s disease progression by 75%, significantly beating analyst expectations. This initially sent shares soaring 248%, with plans underway to file the BLA in the first quarter of 2026.

• The Regulatory Pivot: Analysts expressed surprise at the agency’s change in guidance, noting that the trial design for the AAV gene therapy AMT-130 aligned with the FDA’s own recent publications on pathways for personalized therapies and draft guidance on gene therapies for small populations, which specifically endorse the use of external controls in certain contexts.

Scenarios for the AMT-130 AAV Therapy

AMT-130 is an AAV gene therapy delivered directly into the brain via a minimally invasive surgical procedure, designed to suppress the production of the toxic huntingtin protein. If approved, this AAV therapeutic would be the first genetic treatment for Huntington’s disease.

uniQure stated it is “carefully evaluating” the feedback and intends to “urgently” seek a follow-up meeting with the FDA during the first quarter of 2026.

Industry analysts suggest several possible scenarios for the AAV gene therapy moving forward:

1. Challenging Path: The FDA may require a completely new study, which would significantly delay approval for the AMT-130 AAV therapy.

2. Compromise: A middle ground involving following the existing patient cohort for a longer period and/or enrolling more patients into the ongoing AAV gene therapy studies.

3. Reversal: A potential, though unlikely, reversal of the FDA’s current stance, possibly influenced by external pressure regarding the urgent unmet need for the AAV therapy.