The Food and Drug Administration (FDA) is maintaining its requirement that uniQure conduct a sham-controlled trial for its Huntington’s disease gene therapy, AMT-130, before the agency will review the treatment. A senior FDA official disputed uniQure’s description of the proposed study and addressed concerns about the ethics of such a trial.
“We asked uniQure to take their product and randomize patients to getting the treatment the way they give the treatment, which requires a skin incision, a hole in the skull and an intracranial injection of the product,” said the official during a call with reporters. Fierce Biotech reported on this conversation but did not name the official at the request of the Department of Health and Human Services.
UniQure’s chief medical officer Walid Abi-Saab had previously raised ethical concerns about requiring patients to undergo anesthesia for up to 12 hours and receive a superficial burr hole in their skulls as part of a sham-controlled study. “All of these elements represent risk for these patients,” Abi-Saab stated.
However, according to Thursday’s call, the FDA does not intend for participants in the control group to undergo partial sham burr holes. The official clarified: “We did not ask them to compare against a partial sham burr hole,” adding that instead, uniQure would need to “anesthetize the patient and put one to three nicks in the scalp.”
AMT-130 is administered via surgery directly into brain tissue as a potential treatment for Huntington’s disease—a rare and fatal neurodegenerative disorder. UniQure has cited results from its Phase 1/2 study indicating that AMT-130 slowed disease progression by 75% compared with external controls. Analysts have noted that these results exceeded expectations.
Despite this data, in November 2025, the FDA informed uniQure that it no longer considered evidence from this earlier study sufficient as primary support for approval. UniQure described this stance as a major change from previous feedback received from regulators.
On Thursday’s call, however, an FDA official rejected claims that there had been any shift in policy or prior approval regarding trial design. The official stated: “Did the FDA ever agree to accept this distorted comparison? No,” adding: “I’ve asked our people to look for any written or verbally transcribed or minutes of a meeting that document such a promise, and there is no such promise made.”
The debate over how best to evaluate AMT-130 continues as stakeholders weigh ethical considerations alongside regulatory standards established by longstanding agency policy.
