Regulatory Submission

uniQure to file AMT-130 BLA in Huntington's on accelerated-approval path

The FDA told uniQure the 3-year Phase I/II analysis can support a Huntington's disease BLA, but a confirmatory trial design isn't yet settled ahead of the Q3 2026 filing.

By AppliedXLJuly 13, 2026Trial NCT04120493

Executive Summary

uniQure has cleared FDA agreement to use its multi-year Phase I/II data as the primary evidence for a Huntington's disease BLA, and plans to file under the accelerated-approval pathway in the third quarter.
The design of the confirmatory trial the FDA requires alongside accelerated approval, including whether it swaps a sham-surgery control for a standard-of-care comparator, has not been finalized ahead of the filing.
AMT-130 would be the first gene therapy filed for Huntington's disease targeting the huntingtin gene, with no approved disease-modifying therapy in the setting and only one other direct-target competitor still in early clinical testing.
Multiple FDA designations already granted to the program reflect an agency view of high unmet need in Huntington's disease, though those designations track need rather than predict the filing's outcome.

The regulatory checkpoint

During a Type B meeting (mid-development FDA discussion), the FDA told uniQure that the 3-year analysis from its Phase I/II program would be acceptable as the primary basis of a BLA for accelerated approval of AMT-130 in Huntington's disease. The company said it intends to submit the BLA in the third quarter of 2026. Chief executive Matt Kapusta said the FDA had "agreed that our current clinical data can support a near-term BLA submission". AMT-130 has been granted Regenerative Medicine Advanced Therapy designation, described as the first RMAT designation issued for Huntington's disease, along with Breakthrough Therapy and Fast Track designations. uniQure

What remains open

The FDA also told uniQure it wants to align on the design of the required confirmatory trial before the BLA is submitted, including whether that trial uses a concurrent standard-of-care control rather than the sham-surgery procedure used in the U.S. Phase I/II cohorts. uniQure said it is committed to running the confirmatory study without delay and expects to reach agreement with the FDA on its details before filing. Accelerated approval carries a mandatory confirmatory-trial obligation, and the pathway can be reversed if that trial fails to confirm benefit. uniQure

The underlying data

The proposed primary basis compares cohorts 1 and 2 of the Phase I/II program against a propensity-score-matched external control drawn from the Enroll-HD natural history dataset, under a prespecified statistical analysis plan. In the U.S. study, 26 patients with early manifest Huntington's disease were randomized to a low dose (n=6), a high dose (n=10), or a sham procedure (n=10), with four control patients later crossing over to treatment; the design includes a blinded 12-month core period followed by five years of unblinded follow-up in treated patients. A companion European open-label Phase 1b/2 study enrolled 13 patients. AMT-130 is delivered as a single administration through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum. uniQure

The competitive field

No gene therapy targeting the huntingtin gene has reached a BLA filing in Huntington's disease. Hoffmann-La Roche's SPK-10001 is the nearest direct comparator sharing both the HTT target and gene-therapy modality, and remains in Phase 1/2 testing. Novartis's antisense candidate votoplam has advanced to Phase 3 in the same indication but works through a different mechanism, targeting the huntingtin pre-mRNA transcript rather than delivering a gene-therapy vector. No approved disease-modifying therapy exists for Huntington's disease, and the field spans mechanistically diverse approaches, from gene therapy to antisense oligonucleotides, rather than a single validated modality.

Trial operations

The underlying registry record for NCT04120493 shows a primary completion date that has moved from December 2022 to April 2029, and now to June 2029, alongside enrollment that has been revised between 26 and 44 patients over the trial's history. The trial's status has toggled between Recruiting and Active, not recruiting five times since 2024, most recently landing on Active, not recruiting in October 2025. Those changes reflect a long-running Phase 1/2 program with an extended follow-up structure rather than a readout tied to a near-term primary completion; the regulatory filing draws on the 3-year analysis already generated within that program, not on the registry's stated 2029 completion date. NCT04120493

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.