FDA opens path for uniQure’s Huntington’s gene therapy filing

Dutch gene therapy developer uniQure is preparing to file its Huntington’s disease candidate AMT-130 for accelerated approval in the US, after the Food and Drug Administration signalled it would accept three-year Phase I/II data as the primary basis of a Biologics License Application.

The decision, communicated during a recent Type B meeting – a regulatory discussion used to resolve key development and filing questions – marks a sharp reversal in the regulatory trajectory of AMT-130. uniQure now intends to submit the BLA (Biologics License Application) in the third quarter of 2026, although the company said it still expects final meeting minutes within 30 days and must align with the agency on the design of a confirmatory study before filing.

A game changer in Huntington’s disease

Huntington’s disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. It leads to progressive motor, cognitive and psychiatric symptoms, and there are currently no approved therapies that delay disease onset or slow progression. uniQure estimates that about 75,000 people live with Huntington’s disease across the US, EU and UK.

AMT-130 is designed as a one-time, huntingtin-lowering gene therapy for early manifest Huntington’s disease. Unlike most drugs, AMT-130 is not given by pill or infusion. It is delivered once through MRI-guided brain surgery into the striatum, a region involved in movement and heavily affected by Huntington’s disease. In the US Phase I/II study, 26 patients were randomised to low-dose treatment, high-dose treatment or a sham procedure. A European open-label Phase Ib/II study enrolled another 13 patients.

The key regulatory question is whether the small clinical dataset can support accelerated approval. uniQure’s pivotal analysis compares treated patients with a propensity score-matched external control group derived from Enroll-HD, a natural history dataset, rather than relying on a conventional Phase III placebo-controlled trial.

That approach had become a major point of contention. In March 2026, FDA staff reportedly continued to question the evidence package and strongly recommended another trial involving a control group receiving sham surgery. The latest update suggests the agency is now willing to consider the existing three-year analysis, provided uniQure also commits to a confirmatory study.

The challenge of sham procedure

The confirmatory trial remains the main unresolved issue. uniQure said the FDA is considering a design using concurrent control patients receiving standard-of-care therapy, rather than requiring a sham procedure. This distinction matters for Huntington’s disease because AMT-130 requires brain surgery, making placebo-style controls ethically and practically difficult.

The company has reported that high-dose AMT-130 slowed disease progression by 75% after three years in treated patients compared with an external control group, a result that electrified the Huntington’s community when first disclosed in 2025. The dataset remains small, however, and has not removed all regulatory risk.

The regulatory turnabout triggered a strong market reaction. uniQure shares rose nearly 80% yesterday, as investors reassessed the probability that AMT-130 could reach the US market without a new pre-approval sham-controlled trial.

The case is also being watched beyond Huntington’s disease. The FDA’s change in position is a possible sign of greater flexibility for rare disease programmes, especially where conventional trials are hard to conduct.

The harder line held by the FDA in recent months was closely associated with two high-profile FDA figures: Commissioner Marty Makary and Vinay Prasad, who led the agency’s biologics division and had become a lightning rod for criticism from biotech investors and rare disease advocates. Makary publicly defended the agency’s tougher stance on accelerated approvals, while Prasad was widely seen as driving a more rigorous approach to rare disease and gene therapy reviews. His planned departure from the FDA in April 2026 was followed by a rally in several affected biotech stocks, including uniQure, as investors speculated that the agency might become more flexible again.

For uniQure, the immediate next step is no longer generating a fresh pre-approval efficacy dataset, but securing agreement on the confirmatory pathway. AMT-130 has already received RMAT, Breakthrough Therapy and Fast Track designations from the FDA, and the company has also been preparing a UK marketing authorisation application after a pre-submission meeting with the MHRA.

The latest FDA position does not amount to an approval, and the agency could still judge the final BLA package insufficient. But it reopens a near-term regulatory path for what could become the first disease-modifying therapy for Huntington’s disease and a key test case for how far regulators are willing to go in accepting external controls and small datasets in severe neurodegenerative rare diseases.