Developer, FDA to meet face-to-face on plans for testing Fabry gene therapy
Glafabra, aiming for OK for clinical trials, calls meeting a 'regulatory milestone'
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The U.S. Food and Drug Administration (FDA) has agreed to meet with Glafabra Therapeutics to discuss plans for clinical testing of GT-GLA-S03, the company’s gene therapy candidate for Fabry disease.
The face-to-face meeting, scheduled for July 16, was arranged through the FDA’s INTERACT program, which allows certain developers to receive regulatory feedback before submitting an investigational new drug application (IND) to the agency. Approval of an IND gives developers a green light to begin clinical testing in humans.
Glafabra notes that INTERACT is very competitive; the FDA denies about 70% of meeting requests submitted through it.
“This is a meaningful regulatory milestone. The INTERACT program gives cell and gene therapy developers direct agency feedback at an early development stage, … and acceptance is selective,” Glafabra said in a company press release announcing the July date.
“Feedback from the meeting will directly shape Glafabra’s IND submission, targeted for [the first quarter of] 2027, and is expected to reduce regulatory uncertainty heading into the planned Phase 1/2 trial,” the company stated. If all goes as planned, the developer expects to start enrolling patients in the clinical trial in the third quarter of 2027.
A rare inherited condition, Fabry is caused by mutations that lead to a deficiency of the alpha-galactosidase A (alpha-Gal A) enzyme. This enzyme is normally needed to break down certain fatty molecules, including lyso-Gb3, in the body. People with Fabry lack a functional version of this enzyme, so these fatty molecules build up to toxic levels in cells, ultimately driving disease symptoms.
The current standard of care for Fabry disease is enzyme replacement therapy (ERT), in which a working version of the alpha-Gal A enzyme is administered into the bloodstream. But this requires patients to undergo regular infusions, and they often have to schedule their lives around them.
Gene therapy for Fabry designed to work for up to 5 years
Glafabra says on a company webpage that its investigational treatment is “a novel, long-lasting type of cell-based gene therapy clinically demonstrated to endure up to [five] years from one dose.”
GT-GLA-S03 targets hematopoietic stem cells (HSCs), which are cells that live in the bone marrow and are responsible for making new blood cells and immune cells. The gene therapy works by collecting a patient’s HSCs, modifying them to produce functional alpha-Gal A enzyme, and then infusing the modified cells back into the patient to provide a long-lasting supply of the enzyme throughout the body. Prior to the infusion, patients undergo a conditioning regimen that aims to eliminate some existing HSCs and make room for the modified cells.
According to the company, this “technology provides a durable solution for patients that is easy-to-take … and delivered in an outpatient setting. The result is an attractive therapy for patients allowing them to live a more normal life.”
In a previous investigator-sponsored Phase 1 clinical trial (NCT02800070), five men with Fabry were treated with GT-GLA-S03. Four of them were able to receive conditioning as a same-day outpatient procedure (i.e., without hospitalization). No serious side effects related to the therapy were reported, and blood levels of lyso-Gb3 were reduced by 48% relative to levels without ERT, according to the company.
After five years of follow-up, all but one of the patients maintained lyso-Gb3 levels below the elevated threshold, the company noted.
Glafabra also noted that GT-GLA-S03 was granted orphan drug status by the FDA, a designation that aims to incentivize the development of treatments for rare diseases by providing perks, such as seven years of market exclusivity if ultimately approved.
