First patient dosed in uniQure trial of AMT-191 gene therapy for Fabry
Study still recruiting men with suboptimal ERT response at site in Virginia
The first patient has been dosed in uniQure’s U.S. Phase 1/2a clinical trial of AMT-191, its gene therapy candidate for Fabry disease.
The clinical trial, an open-label study (NCT06270316) focused on safety and early efficacy, is still recruiting about 12 adult male patients at a site in Fairfax, Virginia. Eligible men will have had a suboptimal response to enzyme replacement therapy (ERT). An open-label trial means that both researchers and participants know what treatment is being administered.
“We are very pleased to begin patient dosing for AMT-191 in Fabry disease, marking a significant milestone in this year’s goal to advance three new gene therapy candidates into clinical studies,” Walid Abi-Saab, MD, chief medical officer of uniQure, said in a company press release.
AMT-191 is designed as one-time gene therapy for Fabry
In the trial, six participants will receive a low dose (6×1013 genome copies per kilogram, gc/kg) of AMT-191, while the other six will be given a high dose (3×1014 gc/kg). The experimental therapy will be delivered in a single administration intravenously, or into the vein. Patients will continue their standard ERT until the criteria for withdrawal has been reached, and will be followed for two years after dosing.
Preliminary indicators of efficacy will be evaluated by assessing the levels of the alpha-galactosidase A (alpha-Gal A) enzyme. This enzyme plays a crucial role in Fabry disease, as its deficiency is the hallmark characteristic of the condition.
“Our trial is designed to capture well-established endpoints in Fabry disease and to rapidly generate clinical proof-of-concept data for AMT-191 with a differentiated product profile relative to other Fabry programs in clinical development,” Abi-Saab said.
Fabry disease is caused by mutations in the GLA gene, which contains the instructions to produce alpha-Gal A. This enzyme works to break down fatty molecules like globotriaosylceramide (Gb3) inside lysosomes, the cell compartments that are responsible for recycling cellular waste.
Mutations associated with Fabry lead to insufficient levels of functional alpha-Gal A, which causes the accumulation of toxic levels of fatty molecules throughout the body, including the heart and kidney, leading to organ damage.
Our trial is designed to capture well-established endpoints in Fabry disease and to rapidly generate clinical proof-of-concept data for AMT-191.
AMT-191 is a one-time gene therapy that delivers a working version of the GLA gene directly to liver cells. It does so by using a lab-modified, harmless adeno-associated virus 5 (AAV5) as a capsid, or protein shell, to deliver the functional gene into liver cells. AAV5 technology is also used in Hemgenix, a recently approved gene therapy for hemophilia B that was originally developed by uniQure and has shown a favorable long-term safety profile, according to the company.
uniQure also is developing the gene therapy AMT-130 for Huntington’s disease. Clinical studies are also in preparation for other disorders, including amyotrophic lateral sclerosis.
The company is pleased to be “building on [its] momentum” by advancing the Fabry trial, according to Matt Kapusta, CEO of uniQure.
“This achievement marks an exciting period for the company as we advance additional programs into clinical trials this year,” Kapusta said.
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