uniQure Receives FDA Regenerative Medicine Advanced Therapy Designation for Investigational Gene Therapy in Huntington’s Disease

uniQure N.V. recently announced the US FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation for its investigational gene therapy AMT-130 for the treatment of Huntington’s disease. The FDA granted RMAT designation based on the potential of AMT-130 to address the major unmet medical need among patients with Huntington’s disease. The designation follows the FDA’s review of interim Phase 1/2 clinical data for AMT-130 announced in December 2023 and is based on an analysis comparing these 24-month clinical data to a non-concurrent criteria-matched natural history cohort.

“We’re thrilled to receive the first ever RMAT designation for an investigational therapy for Huntington’s disease,” said Matt Kapusta, Chief Executive Officer of uniQure. “This achievement is a significant milestone for the program and supports the potential for AMT-130 to address the high unmet medical need of those suffering from this devastating disease.”

“The RMAT designation, which was based on the comparison of the two-year AMT-130 data to a natural history cohort, marks a promising start to our FDA interactions,” added Walid Abi-Saab, Chief Medical Officer of uniQure. “Importantly, RMAT designation allows for increased collaboration with the FDA to accelerate development, potentially facilitating earlier access for patients with life-threatening medical conditions. I’m incredibly proud of the team at uniQure for this accomplishment, and we look forward to presenting updated interim data from our ongoing Phase 1/2 studies in the middle of the year.”

RMAT designation was created as part of the 21st Century Cures Act to expedite the development and review processes of regenerative medicine therapies. A regenerative medicine therapy can be eligible for RMAT designation if it is intended to treat, modify, reverse, or cure a serious condition, and if preliminary clinical evidence indicates the drug has the potential to address unmet medical needs for such a condition. Receiving RMAT designation offers sponsor companies all the benefits of the fast track and breakthrough therapy designation programs, allowing for early, close, and frequent interactions with the FDA. This includes opportunities for early agency interactions to discuss the use of surrogate or intermediate endpoints, potential approval pathways including ways to support accelerated approval, and other opportunities to expedite development.

uniQure expects to provide updated interim data from the ongoing Phase 1/2 US and European studies of AMT-130 in the middle of 2024. The interim update will include up to three years of follow-up on 29 treated patients, 21 of which will have been followed for at least 2 years.

The US Phase 1/2 clinical trial of AMT-130 for the treatment of Huntington’s disease is exploring the safety, tolerability, and efficacy signals in 26 patients with early manifest Huntington’s disease split into a 10-patient low-dose cohort followed by a 16-patient high-dose cohort. Patients are randomized to treatment with AMT-130 or an imitation (sham) surgery. The multi-center trial consists of a blinded 12-month core study period followed by unblinded long-term follow-up for a period of up five years. A total of 16 patients in the clinical trial were randomized to treatment and received a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). An additional four control patients in the high-dose cohort crossed over to treatment following the core study period. Additional details are available on www.clinicaltrials.gov (NCT04120493).

The European, open-label Phase 1b/2 study of AMT-130 enrolled 13 patients with early manifest Huntington’s disease across two dose cohorts; a low-dose cohort of six patients and a high-dose cohort of seven patients. Together with the US study, the European study is intended to establish safety, proof of concept, and the optimal dose of AMT-130 to take forward into Phase 3 development or into a confirmatory study should an accelerated registration pathway be feasible.

Patient dosing is ongoing in a third cohort of up to 12 patients to further evaluate both doses of AMT-130 in combination with perioperative immunosuppression. Enrollment in this third cohort is expected to be completed in the second half of 2024. AMT-130 is uniQure’s first clinical program focusing on the central nervous system incorporating its proprietary miQURE platform.

Huntington’s disease is a rare, inherited neurodegenerative disorder that leads to motor symptoms including chorea, behavioral abnormalities and cognitive decline resulting in progressive physical and mental deterioration. The disease is an autosomal dominant condition with a disease-causing CAG repeat expansion in the first exon of the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain. Despite the clear etiology of Huntington’s disease, there are currently no approved therapies to delay the onset or to slow the disease’s progression.

uniQure’s mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of our gene therapy for hemophilia B – a historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. We are now leveraging our modular and validated technology and manufacturing platform to advance a pipeline of proprietary gene therapies for the treatment of patients with Huntington’s disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe diseases. For more information, visit www.uniQure.com.