uniQure Files BLA for AMT-130 Gene Therapy in Huntington’s Disease

uniQure has submitted a Biologics License Application (BLA) to the U.S. FDA seeking accelerated approval for ifezuntirgene inilparvovec (AMT-130), an investigational gene therapy for Huntington’s disease. The company has also submitted a Marketing Authorisation Application (MAA) to the U.K. Medicines and Healthcare products Regulatory Agency (MHRA). Both filings are supported by three-year Phase I/II clinical data showing a slowing of disease progression.

Regulatory Filings Advance AMT-130

The BLA marks a major regulatory milestone for AMT-130, a one-time gene therapy being developed for Huntington’s disease, an inherited neurodegenerative disorder characterized by progressive motor, cognitive, and behavioral decline. uniQure has requested Priority Review from the FDA. If granted, the review period would be shortened to six months following the agency’s standard 60-day BLA filing review period.

The parallel MAA submission advances the regulatory pathway in the U.K. Both applications are supported by a three-year analysis from the Phase I/II program that compared treated patients with a propensity score-matched external control group derived from the Enroll-HD natural history database.

Gene-Silencing Approach Targets Huntingtin

AMT-130 uses uniQure’s proprietary miQURE gene-silencing platform to target the huntingtin (HTT) gene. The therapy incorporates a microRNA specifically designed to silence HTT and the potentially highly toxic exon 1 protein fragment implicated in Huntington’s disease.

Patients receive a single administration through MRI-guided, convection-enhanced stereotactic neurosurgery directly into the caudate and putamen within the striatum, brain regions substantially affected by the disease.

Huntington’s disease results from an autosomal dominant CAG repeat expansion in the first exon of HTT, leading to production and aggregation of abnormal huntingtin protein in the brain. Current therapies address symptoms but do not delay disease onset or slow underlying disease progression.

Phase I/II Program Details

The clinical data supporting the regulatory filings come from multiple Phase I/II cohorts:

• U.S. randomized study (NCT04120493): 26 patients received either a low dose of AMT-130 (n=6), a high dose (n=10), or a sham procedure (n=10). Four patients from the sham group subsequently crossed over to treatment after approximately 12 months.
• European open-label study (NCT05243017): 13 patients received either a low dose (n=6) or high dose (n=7).
• Additional cohorts: A 12-patient cohort evaluated both doses in combination with immunosuppression, while a six-patient U.S. cohort is evaluating the high dose in patients with lower striatal volumes than those enrolled in earlier cohorts.

The three-year comparative analysis showed slower disease progression among AMT-130-treated patients relative to the propensity score-matched external control. The filing announcement did not provide additional detailed efficacy or safety results.

Four-Year Data Expected in Q3 2026

Matt Kapusta, CEO of uniQure, described the dual regulatory submissions as an important milestone for the Huntington’s disease community and highlighted continued engagement with the FDA and MHRA as the applications progress.

AMT-130 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), and Fast Track designations from the FDA. It is the first investigational Huntington’s disease therapy to receive both Breakthrough Therapy and RMAT designations.

The next major development milestone is expected before the end of Q3 2026, when uniQure intends to present four-year data from its ongoing Phase I/II studies. The longer-term analysis could provide additional insight into the durability of the observed treatment effect as regulators assess AMT-130’s potential role in slowing Huntington’s disease progression.

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