uniQure Begins Phase I/IIa Trial of AMT-191 for Fabry Disease

On August 15, 2024, uniQure N.V. (NASDAQ: QURE), a leading gene therapy company, announced the dosing of the first patient in a Phase I/IIa clinical trial of AMT-191 for the treatment of Fabry disease. Fabry disease is a rare, inherited genetic condition. The Phase I/IIa study is a multi-center, open-label trial in the United States that includes two dose-escalating cohorts. The study aims to investigate the safety, tolerability, and initial signs of efficacy of AMT-191 in Fabry disease patients.

Dr. Walid Abi-Saab, the Chief Medical Officer of uniQure, expressed satisfaction with the initiation of patient dosing for AMT-191. He highlighted this event as a significant milestone for the company, aligned with their goal of advancing three new gene therapy candidates into clinical trials this year. AMT-191 employs the same AAV delivery technology used in HEMGENIX®, which has demonstrated long-term safety and effectiveness in patients with preexisting neutralizing antibodies to the AAV capsid. The trial aims to quickly generate clinical proof-of-concept data for AMT-191 using well-established endpoints in Fabry disease.

AMT-191 is an experimental AAV5-based gene therapy that utilizes a proprietary, highly potent promoter to deliver a galactosidase alpha (GLA) transgene. This transgene is designed to target the liver to produce the GLA protein. In Fabry disease patients, a pathogenic variant in the GLA gene results in a deficiency of the α-galactosidase A (aGAL-A) enzyme. This deficiency leads to the accumulation of lipids in various cell types, including kidney and heart cells, eventually causing a multi-system disorder. AMT-191 offers a potentially novel, one-time intravenous treatment approach for Fabry disease.

The Phase I/IIa clinical trial of AMT-191 is being conducted in multiple centers across the United States. The trial includes two cohorts, each consisting of up to six adult male patients. The low-dose cohort will receive 6×10^13 gc/kg, while the high-dose cohort will receive 3×10^14 gc/kg. Both doses are administered through a one-time intravenous infusion. Patients will continue their regular enzyme replacement therapy until they meet the criteria for withdrawal and will be monitored for 24 months. The trial will assess the safety, tolerability, and early signs of efficacy by measuring the expression of the lysosomal enzyme aGLA-A.

Matt Kapusta, the Chief Executive Officer of uniQure, described this achievement as an exciting period for the company. He emphasized the company's focus on advancing additional programs into clinical trials this year. uniQure is actively engaging with the FDA to pursue an expedited clinical pathway for AMT-130 in Huntington’s disease. The company is also initiating new clinical studies in temporal lobe epilepsy and SOD1-ALS. With a strong financial position and extended runway through the end of 2027, thanks to multiple cost reduction initiatives, uniQure is well-positioned to achieve key value-creating milestones.

Fabry disease is an X-linked genetic disorder caused by a deficiency of the GLA enzyme. According to a 2020 study in the Journal of Therapeutics and Clinical Risk Management, the prevalence of Fabry disease is estimated to be between one in 40,000 and one in 117,000 individuals. The current standard treatment involves bi-weekly infusions of enzyme replacement therapy, which has limited effectiveness in many patients due to poor substrate clearance in target organs, particularly the kidney and heart.

uniQure is committed to delivering on the promise of gene therapy by developing single treatments with potentially curative outcomes. The approval of uniQure’s gene therapy for hemophilia B, following more than a decade of research and clinical development, marks a major milestone in genomic medicine. uniQure continues to develop a pipeline of proprietary gene therapies for various severe diseases, including Huntington’s disease, refractory temporal lobe epilepsy, ALS, and Fabry disease.