FDA Agrees AMT-130 Data Can Support Huntington’s Disease BLA

uniQure announced that the U.S. Food and Drug Administration (FDA) has indicated the three‑year analysis from its Phase I/II program may serve as the primary basis for a Biologics License Application (BLA) seeking accelerated approval of AMT‑130.

The feedback, provided during a recent Type B meeting, outlines a clear regulatory pathway for what could become the first disease‑modifying therapy for Huntington’s disease. The company plans to submit the BLA in the third quarter of 2026, with final meeting minutes expected within 30 days.

Confirmatory Study Design Under Discussion

Ahead of filing, FDA and uniQure will finalize the design of a post‑approval confirmatory study. Discussions include the potential use of a concurrent standard‑of‑care control group rather than a sham surgical procedure, reflecting evolving regulatory standards in neurosurgical gene therapy trials.

Gene Therapy Targeting the Root Cause

AMT‑130 is an investigational gene therapy that employs an adeno‑associated virus (AAV) vector to deliver a microRNA construct designed to lower production of mutant huntingtin protein, the genetic driver of Huntington’s disease.

The therapy is administered via a one‑time MRI‑guided neurosurgical infusion into the striatum. Clinical endpoints under evaluation include motor and cognitive function, imaging biomarkers, and huntingtin protein reduction.

Huntington’s Disease

Huntington’s disease results from a CAG repeat expansion in the huntingtin gene, leading to progressive motor dysfunction, cognitive decline, and psychiatric symptoms. Despite decades of research, no approved therapy has slowed disease progression. AMT‑130 has previously received RMAT, Breakthrough Therapy, and Fast Track designations, underscoring the urgent unmet need.

Phase I/II Data Underpin Strategy

The regulatory package will rely on data from the first two cohorts of uniQure’s U.S. Phase I/II study, which enrolled 26 patients with early manifest Huntington’s disease across low‑dose, high‑dose, and sham‑control arms. Four control participants later crossed over to receive treatment. Patients entered a five‑year follow‑up period after the blinded study phase.

Outcomes will be compared with a propensity score‑matched external control population from the Enroll‑HD natural history database, a global observational registry widely used in Huntington’s disease research.

A separate European Phase Ib/II trial enrolled 13 patients across low‑dose and high‑dose cohorts, with additional arms evaluating immunosuppression and treatment in patients with lower striatal volumes. Safety findings to date have shown the therapy to be generally well tolerated, with adverse events consistent with neurosurgical intervention.

Clinical Implications

Chief Executive Officer Matt Kapusta emphasized that FDA’s feedback validates the current clinical package for near‑term submission while enabling continued dialogue on confirmatory requirements. He highlighted the consistency of clinical findings and the urgency of advancing new treatment options for patients.

Global and Future Outlook

While uniQure’s immediate focus is on U.S. accelerated approval, the European program positions the company for potential parallel engagement with EMA. The FDA’s willingness to consider three‑year Phase I/II data marks a pivotal milestone for the Huntington’s disease field.

Over the coming months, attention will center on confirmatory study design, completion of regulatory interactions, and the planned Q3 2026 BLA submission. If approved, AMT‑130 would represent the first gene therapy and one of the first treatments to directly target disease progression in Huntington’s disease potentially shifting the therapeutic paradigm from symptomatic management to disease modification.

What This Means for Patients

For people living with Huntington’s disease and their families, the FDA’s feedback brings AMT-130 a step closer to potential approval. While the therapy remains investigational, the agency’s agreement that existing three-year clinical data could support a BLA submission reduces a major regulatory hurdle and may accelerate access to a treatment that targets the underlying cause of the disease rather than its symptoms.

Current therapies primarily manage movement and psychiatric symptoms but do not slow disease progression. AMT-130 is being developed as a one-time gene therapy intended to lower levels of the mutant huntingtin protein that drives neurodegeneration. If future regulatory review confirms its benefits and safety, the treatment could offer a new option for delaying functional decline in patients with early-stage Huntington’s disease.

Patients should note that FDA has not approved AMT-130, and additional review will be required following the planned BLA submission in the third quarter of 2026. A confirmatory study will also be needed to verify the therapy’s long-term clinical benefit. Nevertheless, the latest regulatory feedback represents an important milestone for a disease area where no approved treatment currently alters the course of disease progression.

Reference

uniQure Announces Plan for BLA Submission for AMT-130 in Huntington’s Disease