Fabry disease treatment AMT-191 trial to enroll 2nd patient group
Enrollment of first set of patients complete; panel recommends study continue
A U.S.-based Phase 1/2a clinical trial testing AMT-191, uniQure’s gene therapy treatment for Fabry disease, has completed enrollment of the first patient group, and the company plans to start recruiting for the second group by the end of March.
Dosing in the trial began in August 2024. The trial’s independent data monitoring committee (IDMC), a panel of external experts tasked with ensuring the safety of trial participants, reviewed data from the first two patients and didn’t find any significant data concerns, uniQure said. The panel recommended that the study continue enrollment and dosing of the second group, which will receive a higher dose of the therapy. The company expects to initiate recruitment for that second group by end of March at the two trial sites in New York and Fairfax, Virginia.
“We are encouraged by the initial pharmacodynamics [effects on the body], biomarkers and safety profile observed to date for AMT-191 as well as the positive outcome of the IDMC review,” Walid Abi-Saab, MD, chief medical officer of uniQure, said in a company press release. “This strengthens our confidence in the potential of AMT-191 to make a meaningful difference in the lives of patients with Fabry disease. We look forward to advancing to the second [group] in this important clinical program.”
Fabry disease occurs due to mutations in the GLA gene that result in a lack of working alpha-galactosidase A (alpha-Gal A), an enzyme responsible for breaking down fatty substances. This alpha-Gal A shortage results in the toxic buildup of fatty molecules throughout the body, and the accumulation affects organs including the heart and kidneys, ultimately damaging them.
“Fabry is a debilitating disease that continues to represent a significant unmet medical need,” Abi-Saab said.
Enzyme production
AMT-191 is a single-dose gene therapy that uses a modified, harmless adeno-associated virus to introduce a working version of the GLA gene into liver cells. This is expected to promote the production of the missing enzyme, normalize levels of fatty substances, and ease Fabry symptoms.
The medication received orphan drug and fast track designation from the U.S. Food and Drug Administration (FDA) for Fabry disease.
The Phase 1/2 study (NCT06270316) is evaluating the safety, tolerability, and preliminary efficacy AMT-191 when administered directly into the bloodstream, in two groups of up to six men with Fabry disease, ranging in age from 18-50.
The first group is receiving a low treatment dose (60 trillion genome copies per kilogram, gc/kg) of AMT-191, while those to be enrolled in the second group will be treated with a high dose (300 trillion gc/kg).
Participants can continue to receive regular enzyme replacement therapy, which delivers a lab-made version of alpha-Gal A directly into the bloodstream, until criteria for withdrawal are met.
Patients will be followed for up to two years, and the therapy’s exploratory efficacy will be measured by analyzing alpha-Gal A levels. The trial is expected to end in 2027.
About the Author
