FDA grants priority review to gene therapy for Huntington’s
Final decision on ifezuntirgene inilparvovec expected by May 1 of next year
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The U.S. Food and Drug Administration (FDA) has agreed to review uniQure’s application seeking accelerated approval of AMT-130, a gene therapy candidate for Huntington’s disease that is now called ifezuntirgene inilparvovec.
“The FDA’s acceptance of our [application] for review marks an important milestone for the Huntington’s disease community,” Matt Kapusta, uniQure‘s CEO, said in a company press release. “Backed by compelling data from our Phase I/II studies, we believe ifezuntirgene inilparvovec has the potential to become the first disease modifying treatment for Huntington’s disease.”
The application, submitted to the agency two months ago, was granted priority review, which shortens the review time from a standard 10 months to six months. A final decision is expected by May 1, 2027.
The FDA also said it is tentatively planning to discuss the application at an advisory committee meeting, a public gathering of independent experts and patient representatives who evaluate available data and provide recommendations to the agency.
Accelerated approval allows an experimental therapy to be marketed based on preliminary evidence of its efficacy. Full approval is dependent on additional clinical trial data confirming the therapy’s clinical benefits.
FDA, uniQure agree on confirmatory trial design
The company also announced alignment with the FDA on the design of a potential confirmatory trial to potentially support ifezuntirgene inilparvovec’s full approval. About 200 Huntington’s patients are expected to be enrolled in that study, and in addition to standard of care, two-thirds will receive the one-time gene therapy. The company expects that patient screening in the U.S. will start by year’s end.
The main goal will be to assess changes in patients’ daily functioning using the Total Functional Capacity (TFC) scale after three years. The TFC measures functioning across five domains: occupation, finances, household chores, daily activities, and care level.
“With the FDA’s priority review underway, we will work in conjunction with the Agency, clinicians, and the Huntington’s community to support the review process,” 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.”
A similar application has been submitted to regulatory authorities in the U.K.
Therapy designed to suppress production of normal, mutated protein
In Huntington’s, genetic mutations lead to an abnormal version of the huntingtin protein, which is thought to cause nerve damage and drive disease symptoms. Despite a clear cause of Huntington’s, there are no therapies to delay the disease’s onset or to slow its progression.
Ifezuntirgene inilparvovec is a one-time gene therapy administered directly into the brain via a surgical procedure. It’s designed to suppress the production of both normal and mutated huntingtin in the brain, which is expected to slow disease progression and ease symptoms.
The therapy received several FDA designations meant to accelerate its clinical development and regulatory review, including fast track, breakthrough therapy, and regenerative medicine advanced therapy designations.
Approval application supported by clinical trial data
The approval application is supported by three years of data from two Phase 1/2 clinical trials testing the therapy in adults, ages 25-65, with early-stage Huntington’s: one in the U.S. (NCT04120493) and one in Europe (NCT05243017).
Score changes in the composite Unified Huntington’s Disease Rating Scale — a standard measure of disease progression — were compared with those of an external group of untreated patients in Enroll-HD (NCT01574053), the world’s largest observational study involving people with the rare disease.
This external control group was matched to patients treated with ifezuntirgene inilparvovec in terms of several pre-treatment demographic and clinical features.
Data showed that three years after treatment, the high dose of ifezuntirgene inilparvovec was associated with a 75% slower disease progression.
Before submitting an application for ifezuntirgene inilparvovec, the FDA had requested that uniQure run an additional clinical trial to provide more supporting data. Following a meeting with the company, however, the agency withdrew the request and agreed that the data collected so far was sufficient to support an approval application.
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