FDA grants orphan designation to new Fabry cell therapy GT-GLA-S03
Approach uses modified stem cells to provide ongoing enzyme supply
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The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to GT-GLA-S03, an experimental cell therapy being developed by Glafabra Therapeutics for Fabry disease.
The FDA gives this designation to investigational therapies for diseases that affect fewer than 200,000 people in the U.S. It offers incentives such as tax credits and fee waivers, as well as seven years of market exclusivity if the therapy is approved. The goal is to encourage companies to develop treatments for rare diseases.
“Granting of the Orphan Drug Designation for GT-GLA-S03 allows us to continue our efforts to develop more effective options for patients suffering with Fabry Disease,” Chris Hopkins, PhD, CEO of Glafabra, said in an email to Fabry Disease News.
Next steps toward clinical development
According to a company press release, the designation marks an early milestone in Glafabra’s plans to seek FDA approval of GT-GLA-S03. Next steps include meeting with the FDA to pursue additional designations that could speed development, as well as securing clearance to launch a clinical trial the company hopes to begin in early 2027 at the University of Utah.
“The FDA’s decision validates the urgent need for a more durable and predictable treatment option for the Fabry community,” said Brian Shayota, MD, director of metabolic services at University of Utah Health/Primary Children’s Hospital, who is set to lead the upcoming study. “Our clinical program … is uniquely positioned to demonstrate how steady-state enzyme expression can stabilize organ function and free patients from the burden of bi-weekly infusions.”
Fabry disease is caused by mutations that lead to a deficiency of the alpha-galactosidase A (alpha-Gal A) enzyme, which helps break down certain fatty molecules. Without a functional version of this enzyme, fatty substances build up to toxic levels in cells, ultimately causing organ damage and disease symptoms. Standard treatment involves enzyme replacement therapy (ERT), in which a functional version of the alpha-Gal A enzyme is given as a medicine.
GT-GLA-S03 works by collecting a patient’s hematopoietic stem cells, which reside in the bone marrow and are responsible for making new blood cells and immune cells. These blood stem cells are genetically modified using Glafabra’s Live-cel platform to produce a functional alpha-Gal A enzyme, then infused back into the patient. The goal is for these modified cells to give rise to immune cells that provide a long-lasting supply of the enzyme throughout the body, reducing the need for regular ERT infusions.
Early trial shows enzyme activity, stable kidney function
In a pilot Phase 1 clinical trial (NCT02800070), five men with Fabry disease received treatment with GT-GLA-S03. Findings indicated that the therapy increased levels of the alpha-Gal A enzyme while decreasing levels of toxic fatty buildups, with stable kidney function observed over five years of follow-up.
“The benefits were many! I have felt the BEST I’ve felt in my life. At one point, my wife and I realized we were forgetting I had Fabry at all,” one participant in the pilot study said in the Glafabra press release. Another study participant is quoted: “After the cell therapy, I stopped ERT with benefits to productivity, travel flexibility and general schedule flexibility.”
Glafabra plans to seek FDA platform designation for its therapeutic approach, while also developing this method for other lysosomal storage disorders, including Pompe and Gaucher diseases.
