Glafabra Therapeutics Receives FDA Orphan Drug Designation for GT-GLA-S03, Advancing a Redosable Cell Therapy for Fabry Disease

Glafabra Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to GT-GLA-S03, its lead cell therapy candidate for classic Fabry disease.

ODD is granted to therapies targeting diseases affecting fewer than 200,000 Americans, ODD unlocks seven years of post-approval market exclusivity, exemption from FDA user fees (approximately $4.68 million for FY2026), and federal tax credits for qualified clinical trial expenses. It is also the first completed milestone in Glafabra’s U.S. regulatory roadmap - next comes an FDA INTERACT meeting, request for fast-track designation, request for Rare Pediatric Disease Designation, request for Pre-IND meeting, and obtaining an open IND so a clinical trial can start at University of Utah Health in early 2027. Ultimately, Glafabra intends to pursue regulatory recognition of the Live-cel™ approach as a platform technology for multiple lysosomal storage disorders.

ABOUT FABRY DISEASE

Fabry disease is a rare inherited condition in which one enzyme - alpha-galactosidase A - is defective, causing progressive accumulation of toxic metabolites, such as lyso-Gb3, in the kidneys, heart, nervous system, and skin. Over time, that buildup leads to kidney failure, heart disease, neuropathic pain, and stroke, and often leading to progressive organ damage and reduced life expectancy if left untreated.

Today’s standard of care is Enzyme Replacement Therapy (ERT) - an IV infusion patients receive every two weeks for the rest of their lives. That’s 26 clinic visits per year, indefinitely. Some patients develop immune reactions that reduce the effectiveness of ERT over time. Annual cost can exceed $300,000 per patient.

THE LIVE-CEL™ PLATFORM: A LIVING ENZYME FACTORY

Instead of delivering the missing enzyme from outside the body on a recurring schedule, GT-GLA-S03 engineers the patient’s own cells to produce it from within. A patient’s immune stem cells are collected, genetically modified to carry a working copy of the GLA gene, and returned in a single infusion. The introduced cells settle in the bone marrow and produce blood cells that go everywhere in the body to provide an ongoing enzyme source. Through a natural sharing mechanism called cross-correction, the cells that are nearby can actively take up the enzyme and use it to stop the buildup of toxic metabolites.

Fabry disease belongs to a family of lysosomal storage disorders (LSDs) - diseases where a defective enzyme inside the cell’s recycling system causes toxic waste to accumulate and damage organs over time. In the future, Glafabra’s future plans to pursue platform designation with the FDA will apply their method to treat not only Fabry disease, but many of the 59 different LSDs, such as Pompe and Gaucher diseases.

Unlike other gene therapies, GT-GLA-S03 is designed to be redosable and outpatient-compatible, using a conditioning protocol that avoids full bone marrow ablation. Based on preliminary clinical data, a single treatment is expected to last approximately five years - 130 times longer between doses than bi-weekly ERT.

FIVE YEARS OF HUMAN CLINICAL EVIDENCE

GT-GLA-S03 has already been tested in patients. The Canadian pilot trial (NCT02800070), conducted by co-inventors Dr. Jeffrey Medin and Dr. Ronan Foley, and their team, followed five Fabry patients for five years - with initial results published in 2021 in Nature Communications (PMID 33633114) with related supporting and follow-up studies (PMIDs 36816757, 39794302, 40812318).

Safe: No treatment-related serious adverse events were observed, and key clinical markers of cardiac and renal function remained stable over five years. Effective: Plasma lyso-Gb3 levels decreased by approximately 48%, accompanied by stabilization of estimated glomerular filtration rate (eGFR). Durable: Therapeutic effect was sustained through five years of follow-up in all treated participants.

“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.” — Canadian trial participant

“After the cell therapy, I stopped ERT with benefits to productivity, travel flexibility and general schedule flexibility.” — Second Canadian trial participant

U.S. CLINICAL PROGRAM: UNIVERSITY OF UTAH HEALTH

Glafabra’s planned U.S. Phase 1/2 trial will be led by Dr. Brian Shayota, MD, MPH - Director of Metabolic Services at University of Utah Health and Primary Children’s Hospital, and an experienced principal investigator in gene therapy for rare inborn errors of metabolism. The University of Utah is a NORD-designated Center of Excellence in Medical Genetics. Clinical manufacturing, data coordination, and regulatory support are provided by CellReGen™, the Utah Data Coordinating Center, and Uncommon Cures.

“The FDA’s decision validates the urgent need for a more durable and predictable treatment option for the Fabry community. Our clinical program in Utah is uniquely positioned to demonstrate how steady-state enzyme expression can stabilize organ function and free patients from the burden of bi-weekly infusions.” — Dr. Brian Shayota, MD, MPH — Director of Metabolic Services, University of Utah Health / Primary Children’s Hospital