uniQure has submitted a Biologics License Application (BLA) to the FDA for accelerated approval of ifezuntirgene inilparvovec (AMT-130), an investigational gene therapy for Huntington disease. The company also submitted a Marketing Authorisation Application (MAA) for the therapy to the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA).1
uniQure has requested priority review for the BLA, which, if granted, would shorten the FDA review cycle to 6 months following the agency's 60-day BLA filing review period. Ifezuntirgene inilparvovec is the first investigational Huntington disease therapy to receive both breakthrough therapy and regenerative medicine advanced therapy (RMAT) designations from the FDA, and it also holds a fast track designation.1
"The submission of licensing applications for ifezuntirgene inilparvovec represents an important milestone for the Huntington disease community," Matt Kapusta, chief executive officer of uniQure, said in a statement.1 Kapusta said the company is grateful to the FDA for its leadership in advancing regulatory science to meet the urgency of the disease and to the MHRA for its commitment to advancing rare disease treatments in the UK, adding that uniQure looks forward to working with both agencies as the applications progress.1
READ MORE: FDA Allows AMT-130 Huntington Disease Data to Support Planned BLA Submission Under Accelerated Approval Pathway
A June regulatory update from the FDA reversed course on a bumpy road to this point for ifezuntirgene inilparvovec, following much back-and-forth between the company and the regulatory body on the viability of the gene therapy, driven mainly by concerns around the use of sham procedures and other methodology and the overall interpretation of data. After a recent Type B meeting between uniQure and the FDA in June, the agency requested additional alignment on the design of a confirmatory study that would follow a potential accelerated approval. According to the company, the FDA indicated that the confirmatory study may evaluate AMT-130 against standard-of-care therapy rather than requiring a sham procedure.
Frequently Asked Questions
What is ifezuntirgene inilparvovec being submitted for?
uniQure has submitted a BLA to the FDA for accelerated approval of ifezuntirgene inilparvovec in Huntington disease, along with an MAA to the UK's MHRA.
How does ifezuntirgene inilparvovec work?
The gene therapy uses uniQure's miQURE platform to deliver a microRNA designed to silence the huntingtin gene, administered as a single dose via MRI-guided stereotactic neurosurgical delivery into the striatum.
What data support the submissions?
The submissions are supported by a 3-year data analysis from the phase 1/2 clinical program showing slowed disease progression compared with a propensity score-matched external control from the Enroll-HD natural history database.
Ifezuntirgene inilparvovec trial design and 3-year data
The BLA and MAA are supported by a previously announced 3-year data analysis from the phase 1/2 clinical program, compared with a propensity score-matched external control derived from the Enroll-HD natural history database.1 uniQure is conducting 2 multicenter phase 1/2 studies evaluating the safety, tolerability, and efficacy of ifezuntirgene inilparvovec in Huntington disease (NCT05243017; NCT04120493).1
The US randomized study enrolled 26 patients who received a single administration of ifezuntirgene inilparvovec: 6 at a low dose and 10 at a high dose, and 10 who received a sham procedure; 4 sham patients later crossed over to treatment at approximately 12 months. The European open-label study enrolled 13 patients, 6 at a low dose and 7 at a high dose. A third cohort of 12 patients explored both doses combined with immunosuppression, and a fourth cohort of 6 US patients is evaluating the high dose in patients with lower striatal volumes than those enrolled in earlier cohorts. The 3-year analysis showed ifezuntirgene inilparvovec slowed disease progression relative to the external control.1
At the 2026 American Academy of Neurology (AAN) Annual Meeting in Chicago, investigators presented 3-year follow-up data from the phase 1/2 AMT-130 program (NCT04120493). In the high-dose cohort, treated participants demonstrated a 75% slowing of disease progression on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) compared with matched external controls, alongside favorable trends across motor, cognitive, and functional measures. Investigators also reported reductions in cerebrospinal fluid neurofilament light chain (NfL), a biomarker of neurodegeneration, while no new long-term safety concerns emerged during follow-up.
During the meeting, study author Victor Sung, MD, professor of neurology and director of the Division of Movement Disorders at the University of Alabama at Birmingham, spoke with NeurologyLive about the implications of the findings. In the discussion, Sung explained the rationale and delivery approach behind AMT-130, reviewed the key clinical and biomarker outcomes observed through 3 years, and discussed what these early signals may mean for the future development of disease-modifying therapies in Huntington disease.
