The biotechnology company uniQure has reached a significant milestone in its development of AMT-191, an investigational gene therapy for Fabry disease, with the completion of enrollment in the first cohort of its Phase I/IIa clinical trial. The trial's Independent Data Monitoring Committee (IDMC) has reviewed safety data from the initial two patients and found no significant safety concerns, clearing the way for progression to the second cohort.
The U.S.-based clinical trial, which began dosing patients in August 2024, is evaluating AMT-191 as a potential one-time treatment for Fabry disease. The study is being conducted at two sites in New York and Fairfax, Virginia, with enrollment in the second cohort expected to begin by the end of March.
"We are encouraged by the initial pharmacodynamics, biomarkers and safety profile observed to date for AMT-191," stated Dr. Walid Abi-Saab, Chief Medical Officer of uniQure. "This strengthens our confidence in the potential of AMT-191 to make a meaningful difference in the lives of patients with Fabry disease."
Understanding AMT-191's Therapeutic Approach
AMT-191 represents a novel approach to treating Fabry disease, a genetic condition caused by mutations in the GLA gene. The therapy utilizes a modified adeno-associated virus to deliver a functional copy of the GLA gene to liver cells. This approach aims to restore the production of alpha-galactosidase A (alpha-Gal A), an essential enzyme that breaks down fatty substances in the body.
The absence of functioning alpha-Gal A in Fabry disease leads to the accumulation of fatty molecules throughout the body, particularly affecting the heart and kidneys. "Fabry is a debilitating disease that continues to represent a significant unmet medical need," Dr. Abi-Saab emphasized.
Trial Design and Progress
The Phase I/IIa study (NCT06270316) is structured to evaluate two distinct dosing levels in male patients aged 18-50 years:
- First cohort: Low dose (60 trillion genome copies per kilogram)
- Second cohort: High dose (300 trillion genome copies per kilogram)
Each cohort will include up to six participants, who may continue their existing enzyme replacement therapy until specific withdrawal criteria are met. The trial will monitor patients for up to two years, with completion expected in 2027.
The study's primary focus is to assess the safety and tolerability of AMT-191 when administered intravenously, while also gathering preliminary efficacy data through measurements of alpha-Gal A levels. The therapy has already received both orphan drug and fast track designations from the U.S. Food and Drug Administration, highlighting its potential significance in addressing this rare genetic disorder.
