uniQure Announces Clinical Update on First Patients in Phase 1/2 Clinical Trial of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease

uniQure N.V. recently announced initial observations on the first four patients enrolled in the lower-dose cohort of its ongoing Phase 1/2 clinical trial of AMT-130 for the treatment of Huntington’s disease. Two of the four enrolled patients received AMT-130, and two patients experienced an imitation (sham) surgery in this randomized, blinded clinical trial being conducted in the United States.

“We are pleased with these data that support the tolerability of AMT-130, a potential one-time gene-therapy approach for Huntington’s disease,” said Ricardo Dolmetsch, PhD, President of Research and Development at uniQure. “Neurofilament light chain, a key biomarker of injury in the brain, trended downward and returned to baseline levels in the treated patients, and structural MRI data are consistent with the safety profile of AMT-130. Based on recommendations of the DSMB and steering committee, we will disclose efficacy data including volumetric MRI changes once all patients in the first two cohorts are unblinded. We look forward to evaluating safety, biomarker and functional data on a larger number of patients and over a longer period during the ongoing study.”

“AMT-130 appears to be generally well tolerated both immediately after surgical administration and at 1 year of follow up in these four patients,” said Jody Corey-Bloom, MD, PhD, Professor of Neurosciences at University of California, San Diego and chairperson of the Data Safety Monitoring Board (DSMB) for AMT-130. “We are encouraged by the early data in two treated patients and will continue to provide comprehensive safety oversight of the program as additional patients are enrolled and the trial expands into Europe.  The DSMB will continue to oversee the conduct of this important program, and will evaluate safety, biomarker, imaging, and functional data as the program advances.”

1-Year Observations on AMT-130

The first four patients were a heterogeneous group representing a spectrum of Stage I-II early manifest disease with 41-44 CAG repeats, baseline Total Functional Capacity scores of 10-13 and Total Motor Scores of 7-23.

• AMT-130 was generally well tolerated in the treated patients at the lower dose of 6×10¹² vector genomes (vg).
• There have been no serious adverse events (SAEs) to date related to AMT-130 in these patients.
• NfL increased as expected immediately following the AMT-130 surgical procedure and returned to baseline in the two treated patients. NfL remained relatively constant in the two untreated control patients.
• Structural magnetic resonance imaging did not reveal any clinically meaningful safety findings in either treated or control patients at 1 year of follow-up.
• Measurements of total and mutant HTT protein in the cerebral spinal fluid of the four patients were highly variable and inconclusive.
• The safety profile of AMT-130 in the low-dose cohort to date supports continued enrollment of patients in the higher-dose cohort of 6×10¹³ vg. Nineteen patients have been enrolled in the clinical trial to date, including 9 of 16 in the higher-dose cohort.

A clinical update on the low-dose cohort of ten patients, largely focused on safety, is expected in the second quarter of 2022 after patient unblinding. Full safety and efficacy data from the first two cohorts in the Phase 1/2 clinical trial are expected in the first half of 2023 after all patients in the higher-dose cohort have achieved 1 year of follow-up.

Planned Expansion of Phase 1/2 Studies of AMT-130

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 a planned 26 total patients with early manifest Huntington’s disease split into a 10 patient, low-dose cohort followed by a 16 patient, higher-dose cohort; patients will be 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 five years. A total of 16 patients in the clinical trial will receive a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen).

uniQure also plans to initiate a third cohort in the ongoing US Phase 1/2 clinical trial in the second half of 2022 that will explore the use of alternative stereotactic navigation systems to simplify placement of catheters for infusions of AMT-130. This will be explored in two steps and include up to 18 additional randomized patients who will receive the higher dose of 6×10¹³ vg.

The European, open-label Phase 1b/2 study of AMT-130 will enroll 15 patients with early manifest Huntington’s disease across two dose cohorts. Screening has been initiated, and the first procedures in the lower-dose cohort are expected to be complete in early 2022. 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.

AMT-130 is uniQure’s first clinical program focusing on the central nervous system (CNS) incorporating its proprietary miQURE platform.

Huntington’s disease is a rare, inherited neurodegenerative disorder that leads to motor symptoms including chorea, and 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 no currently approved therapies to delay the onset or to slow the disease’s progression.

uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary gene therapies to treat patients with hemophilia B, Huntington’s disease, Fabry disease, spinocerebellar ataxia Type 3 temporal lobe epilepsy, Alzheimer’s, Parkinson’s and ALS. For more information, visit www.uniQure.com.