The U.S. Food and Drug Administration has accepted uniQure’s Biologics License Application for ifezuntirgene inilparvovec, the company’s gene therapy candidate for Huntington’s disease, under Priority Review. The agency set May 1 as its target Action date under the Prescription Drug User Fee Act.
If approved, the therapy would be the first treatment shown to modify the course of Huntington’s disease, a fatal inherited neurodegenerative disorder. The FDA has tentatively indicated that it may discuss the application at a future advisory committee meeting, most likely the Cellular, Tissue, and Gene Therapies Advisory Committee. No meeting date had been set.
The decision reverses regulatory opposition that emerged last year and intensified earlier this year. In March, the FDA said data from uniQure’s Phase I/II studies, which compared treated patients with an external control group, did not provide sufficient primary evidence of effectiveness for approval. The agency had recommended a prospective, randomized, double-blind, sham surgery-controlled study.
In June, the FDA accepted the three-year analysis from the Phase I/II studies as the primary basis for a potential accelerated approval application. The studies enrolled patients in the United States and Europe and evaluated the therapy’s effect on measures of Huntington’s disease progression.
Ifezuntirgene inilparvovec uses uniQure’s miQURE gene-silencing platform. Its microRNA is designed to silence the huntingtin gene and the potentially toxic exon 1 protein fragment. The treatment is administered once through MRI-guided, convection-enhanced stereotactic neurosurgical delivery into the striatum, including the caudate and putamen.
uniQure said it has aligned with the FDA on key elements of a confirmatory study. The randomized, standard-of-care trial is expected to enroll approximately 200 patients, with participants assigned in a 2:1 ratio to ifezuntirgene inilparvovec or standard care. Total Functional Capacity at 36 months will serve as the primary endpoint. The company plans to begin screening patients in the United States by the end of 2026.
The application has also received the FDA’s Breakthrough Therapy, Regenerative Medicine Advanced Therapy and Fast Track designations.
The company’s previously reported Phase I/II results showed a statistically significant 75% slowing of disease progression at 36 months on the composite Unified Huntington’s Disease Rating Scale in patients who received the high dose, compared with a propensity score-matched external control from the Enroll-HD natural history database.
More recent four-year results showed a 44% slowing of progression on the composite measure, which was not statistically significant, and a 61% slowing on Total Functional Capacity. uniQure said the functional benefit remained at month 48 and that differences between high- and low-dose groups were consistent with a dose-dependent treatment effect.
The ongoing studies have dosed 51 patients. The U.S. randomized study included 26 patients, while the European open-label study enrolled 13. Additional cohorts evaluated the therapy in combination with immunosuppression and in U.S. patients with lower striatal volumes.
Despite the FDA acceptance, uniQure shares fell 3% to $24.03 at 10:56 a.m. ET, compared with $24.83 at the previous Friday’s close. Investor concerns reportedly included the later-than-expected action date, the four-year efficacy data and continuing safety risks in the ongoing trials.