Uncertainty in Regulatory Future
The U.S. Food and Drug Administration (FDA) has reversed its earlier position on uniQure’s gene therapy candidate for Huntington’s disease, AMT-130, creating uncertainty over the treatment’s regulatory future. The company said Monday that the agency no longer considers the phase 1/2 data sufficient to support a biologics license application (BLA) for approval.
Promising Early Data Met with Optimism
In September, uniQure reported that AMT-130 slowed disease progression by 75% after three years compared with an external control group based on a natural history study. The data came from 17 patients who received a high dose of the therapy. The results were described by experts as “game-changing” and led to a 300% surge in the company’s stock price.
FDA Withdraws Support for Accelerated Approval
Following those results, uniQure reached an agreement with the FDA late last year to submit a BLA through the accelerated approval pathway, using the phase 1/2 data and external control comparisons. However, in a recent pre-BLA meeting, the FDA reportedly withdrew support for that approach. The agency now maintains that the phase 1/2 trial alone does not provide adequate evidence for approval.
“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,” said uniQure CEO Matt Kapusta. He added, “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.”
UniQure described the FDA’s position as a “drastic change” from prior guidance, saying the decision alters plans for filing the application in the first quarter of 2026. The company said it expects to receive final meeting minutes within 30 days and intends to “urgently interact with the FDA to find a path forward for the timely accelerated approval of AMT-130.” Following the announcement, uniQure’s shares dropped 66% in pre-market trading on Monday.
A Pattern of Cautious Approvals
The development marks another instance of the FDA’s cautious approach toward cell and gene therapy approvals. Under the leadership of Vinay Prasad, M.D., at the Center for Biologics Evaluation and Research, the agency has recently declined similar applications. Earlier this year, Capricor Therapeutics’ treatment for a heart condition associated with Duchenne muscular dystrophy was rejected for lacking “substantial evidence of effectiveness.” Capricor CEO Linda Marbán said the decision was unexpected, emphasizing that the company had followed the FDA’s guidance.
Likewise, Replimune’s oncolytic virus therapy for melanoma was denied accelerated approval on similar grounds. The FDA said the phase 1/2 data did not demonstrate sufficient efficacy. Replimune CEO Sushil Patel, Ph.D., stated that these issues had not been raised in previous communications. The company has since refiled its application, with a decision expected by April 2026.
Impact on the Huntington’s Community
The reversal on AMT-130 comes just weeks after optimism within the Huntington’s community. During a September investor call, Sarah Tabrizi, Ph.D., of University College London, described the results as “game-changing” and called them “a beacon of hope” for patients. She highlighted that the 75% improvement, measured by the composite Unified Huntington’s Disease Rating Scale, represented “a huge effect size” that could significantly impact patients’ lives.
While analysts at Stifel described the FDA’s reversal as “very surprising” and “very challenging” for uniQure, they also noted that the company’s experience may reflect broader challenges facing the gene therapy field. UniQure said it remains committed to working closely with the agency to determine next steps for AMT-130’s approval process.
Where Does This Leave AMT-130?
UniQure must now reassess whether additional trials (such as a confirmatory phase 3) will be required before filing a BLA with the FDA. The company may explore regulatory pathways outside the U.S. (such as in the European Union or United Kingdom) in parallel.
Investors will monitor how the FDA treats future gene-therapy candidates, as this decision may signal a stricter evidentiary standard for accelerated approval. The Huntington’s community faces delayed access to what had been a promising option; patient-advocacy groups may increase pressure for regulatory clarity.
The decision raises crucial questions around the use of external-control data in rare-disease trials and whether the FDA will tighten acceptance of such designs.
