First patient in uniQure trial treated with Fabry gene therapy AMT-191

The first patient was treated with AMT-191, a gene therapy candidate for Fabry disease, in uniQure's Phase 1/2a clinical trial in the United States.

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. The eligible men will have demonstrated a suboptimal response to enzyme replacement therapy (ERT). An open-label study means that both researchers and participants know what treatment is being administered.

“We are very pleased to begin dosing AMT-191 for patients with Fabry disease. This is an important milestone in achieving our goal this year of advancing three new gene therapy candidates into clinical trials,” said Dr. Walid Abi-Saab, chief medical officer of uniQure, in a company press release.

Recommended reading

AMT-191 is designed as a one-time gene therapy for Fabry

In the study, six participants will receive a low dose (6×10¹³ genome copies per kilogram, gc/kg) of AMT-191, while the other six received a high dose (3×10¹⁴ gc/kg). The experimental therapy is administered as a single dose intravenously or intravenously. Patients continue standard ERT until criteria for discontinuation are met and are followed for two years after dosing.

Preliminary indicators of effectiveness are determined by determining the level of alpha-galactosidase A (alpha-Gal A). This enzyme plays a crucial role in Fabry disease, since its deficiency is the characteristic feature of the disease.

“Our study is designed to capture well-established endpoints in Fabry disease and rapidly generate clinical proof-of-concept data for AMT-191 with a differentiated product profile compared to other Fabry programs in clinical development,” said Abi-Saab.

Fabry disease is caused by mutations in GLA Gene that contains the instructions for making alpha-Gal A. This enzyme breaks down fat molecules such as globotriaosylceramide (Gb3) in lysosomes, the cellular compartments responsible for recycling cellular waste.

Mutations associated with Fabry syndrome result in a deficiency of functional alpha-Gal A, which leads to the accumulation of toxic amounts of fat molecules throughout the body, including the heart and kidneys, resulting in organ damage.

Our study is designed to capture well-established endpoints in Fabry disease and rapidly generate clinical proof-of-concept data for AMT-191.

AMT-191 is a unique gene therapy that produces a working version of the GLA gene directly into liver cells. It does this by using a laboratory-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 originally developed by uniQure, which the company says has demonstrated a favorable long-term safety profile.

uniQure is also developing the gene therapy AMT-130 for Huntington's disease. Clinical trials for other diseases, including amyotrophic lateral sclerosis, are also in preparation.

The company is looking forward to [its] “Dynamics” through the further development of the Fabry study, says Matt Kapusta, CEO of uniQure.

“This success marks an exciting time for the company as we advance additional programs into clinical testing this year,” said Kapusta.