Gaucher gene therapy FLT201 shows sustained clinical benefits
Phase 1/2 GALILEO study tested therapy on six adults with type 1 disease
Treatment with the experimental gene therapy FLT201 led to sustained clinical benefits that lasted up to 21 months for people with Gaucher disease type 1, according to new clinical trial data.
Spur Therapeutics, the therapy’s developer, presented the findings at the 28th annual meeting of the American Society of Gene and Cell Therapy (ASGCT) in New Orleans.
“These findings highlight the power of our approach to provide gene therapies that set new standards of care for people living with serious diseases,” Pamela Foulds, MD, Spur’s chief medical officer, said in a company press release.
Buoyed by data from the Phase 1/2 GALILEO-1 study (NCT05324943), the company has announced plans to launch a Phase 3 trial to further test FLT201 in Gaucher disease.
“As we prepare to initiate a Phase 3 trial for FLT201, these results strengthen our confidence in its potential to dramatically reduce both the disease and treatment burden for people with Gaucher,” Foulds said.
Gaucher disease is caused by mutations in the GBA1 gene, resulting in a deficiency of an enzyme needed to break down certain fatty molecules called glucocerebrosides (Gb1). Deficits in the enzyme lead these molecules to build up to toxic levels in cells, driving disease symptoms. Gaucher type 1, the most common form of the disease, is typically marked by symptoms such as an enlarged liver and spleen, bone complications, and blood abnormalities, but by an absence of neurological problems.
Producing a more stable enzyme
FLT201 is a gene therapy designed to deliver a modified version of the GBA1 gene to cells to aid the production of a functional and more stable enzyme that can clear toxic buildups of Gb1. The therapy is administered via a one-time infusion into the bloodstream.
GALILEO-1 enrolled six adults with Gaucher type 1 who were on standard Gaucher treatments for at least two years and received a low dose of 4.5 hundred billion vector genomes per kilogram of body weight (vg/kg) of FLT201.
The new data cover four participants who were taken off enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) after dosing. The therapies were stopped within three months of FLT201 treatment, and, as of the data cutoff in March, the four have remained off prior therapies for up to 21 months after dosing.
According to Spur, data show robust reductions in glucosylsphingosine (lyso-Gb1), a fatty molecule derived from Gb1 that serves as a key biomarker of disease burden, that were sustained up to 15 months after stopping standard therapies. One participant who had low lyso-Gb1 levels on prior treatment, has seen the biomarker’s levels stay low for at least 14 months after stopping standard treatment.
Common blood abnormalities in Gaucher disease patients include low hemoglobin, the protein in red blood cells that carries oxygen, and low platelets, which are cell fragments that help blood clot. Data from the four participants showed hemoglobin levels have been steadily in the normal ranges, and platelet counts were stable or improved up to 18 months after stopping ERT or SRT. Collectively, the data indicate “strong safety and efficacy signals up to nearly two years after a single dose,” Foulds said.
The presentation at ASGCT also covered new data on using FLT201 in nonhuman primate animal models. The gene therapy led to stable enzyme levels for more than 3.5 years after a single dose.
Available data from both the animal studies and the Phase 1/2 trial have suggested that some patients develop antibodies against the enzyme after gene therapy treatment, but these seem to be temporary and don’t affect its efficacy.
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