uniQure’s gene therapy AMT-130 has been given a renewed shot at regulatory approval after the FDA dramatically reversed its earlier position on the Huntington’s disease treatment.
The agency now agrees that uniQure’s existing clinical data can support a regulatory submission, walking back its previous demand that the Netherlands-based company conduct an entirely new clinical trial.
That earlier recommendation had been widely criticised by experts, with many in the medical community describing the requirement as both impractical and unethical given the severity of the disease.
The FDA’s prior stance was adopted under former Commissioner Marty Makary and former Director of the Center for Biologics Evaluation Research Vinay Prasad, both of whom have since departed the agency.
uniQure said the FDA’s updated thinking on AMT-130 followed the company’s continued engagement with the agency, communicating the shift during a formal Type B regulatory meeting.
The company now intends to file for accelerated FDA approval in the third quarter of 2026, which could make AMT-130 the first approved treatment for Huntington’s disease if successful.
AMT-130 works by using an engineered virus to deliver micro RNA to brain cells, silencing the gene responsible for producing a toxic protein fragment that drives the progression of Huntington’s disease.
The therapy is administered through a surgical procedure requiring holes to be drilled in the skull, with a microcatheter used to deliver the one-time treatment deep into the brain tissue.
In the high-dose cohort of a Phase 1/2 study, AMT-130 met its primary endpoint at three years, showing 75% slowing of cUHDRS progression versus Enroll-HD propensity-matched external controls, with a P value of .003.
The trial used an open-label design comparing treated patients against a natural history external control, a methodology common in rare disease trials where a placebo is considered unethical.
The FDA has agreed the cUHDRS, a validated multi-domain measure of disease progression, may serve as an intermediate clinical endpoint for accelerated approval in this case.
Analysts at William Blair noted the development as a signal of broader regulatory flexibility, writing that “the current FDA, largely in caretaker mode, appears to be more flexible on regulatory paths for applications where concerns were previously raised.”
Stifel separately noted that four-year data for AMT-130, also expected in the third quarter, is “likely to be important” even if it does not form the primary basis of the biologics licence application.
uniQure CEO Matt Kapusta welcomed the shift, saying: “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.”
The FDA has also indicated it will not necessarily require a sham surgery design for the confirmatory study, and has said it will “work as expeditiously as possible” with uniQure to align on that study design ahead of submission.
AMT-130 already holds RMAT, Breakthrough Therapy, and Fast Track designations from the FDA, and uniQure has also been preparing a UK marketing authorisation application following a pre-submission meeting with the MHRA.
The reversal does not constitute approval, and the agency could still find the final biologics licence application package insufficient when it is formally reviewed.
Nevertheless, the decision reopens a near-term regulatory path for what could become the first disease-modifying therapy for Huntington’s disease, a milestone with significant implications for rare neurodegenerative disease treatment.