FDA grants priority review to uniQure Huntington's gene therapy

The U.S. Food and Drug Administration accepted uniQure’s biologics license application for ifezuntirgene inilparvovec (AMT-130), an investigational gene therapy for Huntington’s disease, and granted it priority review with a Prescription Drug User Fee Act target action date of May 1, 2027. The application was submitted under the Accelerated Approval pathway.

uniQure said the FDA’s acceptance letter states the agency is tentatively planning to discuss the application at an advisory committee meeting, and the company will be notified once dates and timelines are finalized. Acceptance starts the FDA's substantive review; it does not permit sales or confirm that the evidence meets the approval standard.

The BLA is supported by 36-month results from the Phase I/II trials, compared against a matched external control drawn from the Enroll-HD natural history database using propensity scores. The Phase I/II studies have dosed 51 patients in total, including a U.S. randomized study with low-dose, high-dose and sham-procedure groups and a European open-label study.

uniQure noted that a September update came after the BLA was submitted and was not part of the original filing; it added more patients to the three-year high-dose analysis, bringing the count to 15. In that group, the composite Unified Huntington’s Disease Rating Scale score fell by 0.28 points, while the updated external control showed a decline of 1.39 points, giving a nominal p-value of 0.005. The four-year analysis of 12 high-dose patients found no statistically significant difference on the composite score (p=0.144), but Total Functional Capacity had a nominal p-value of 0.008. Five patients in the high-dose group experienced serious central nervous system inflammation events related to treatment; all resolved. A suicide in a low-dose patient was judged unrelated to the therapy.

The confirmatory trial will be randomized, compare ifezuntirgene inilparvovec to standard care, and enroll about 200 patients in a two-to-one allocation, with Total Functional Capacity as the primary endpoint measured at 36 months, according to design elements that uniQure and the FDA have aligned on. Patient screening in the U.S. is planned by the end of 2026. Chief executive Matt Kapusta said the confirmatory trial “remains a key priority, with screening anticipated to begin by year end and the study is expected to be well underway by the time of potential approval”.

Ifezuntirgene inilparvovec is a gene-silencing therapy that uses a miRNA designed to silence the huntingtin gene and the potentially toxic exon 1 protein fragment, delivered once through MRI-guided convection-enhanced stereotactic neurosurgery directly into the striatum. The candidate holds Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA.

Priority review shortens the action goal to six months, versus ten months for standard review, but the scientific and medical criteria for approval remain unchanged. uniQure said no approved therapy currently delays onset or slows progression of Huntington’s disease. uniQure states that ifezuntirgene inilparvovec, if cleared, would become the first therapy to modify the course of Huntington’s disease worldwide.