Sangamo seeks accelerated US approval of gene therapy for Fabry
Company advances FDA application following positive study data
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Sangamo Therapeutics said it advanced the rolling submission of a biologics license application (BLA) seeking U.S. accelerated approval of its gene therapy candidate isaralgagene civaparvovec (formerly ST-920) for Fabry disease, following positive data from a clinical trial.
Accelerated, or conditional, approval allows experimental therapies to reach the market based on early evidence suggesting they are likely to benefit patients. Full approval from the U.S. Food and Drug Administration (FDA) depends on additional clinical trial data confirming the treatment’s benefit.
The company is seeking approval through a rolling review process, which allows sections of a BLA to be filed as they are completed rather than waiting until the entire dossier is finalized. Sangamo, which started the application process earlier this year, announced in a company press release that it has now submitted the preclinical and clinical modules of the application to the FDA for review.
A companion diagnostic test has also been submitted to the FDA’s Center for Devices and Radiological Health and accepted for review through the agency’s Premarket Approval pathway, the company said. If approved, the test would be used to screen patients before treatment to determine whether they are suitable candidates for the therapy.
Fabry is caused by mutations in the gene that provides instructions to make an enzyme called alpha-galactosidase A (alpha-Gal A). Without a working version of this enzyme, certain fatty molecules build up to toxic levels in the body’s cells, causing damage to the kidneys and other organs.
Single infusion aims to help body produce enzyme
A mainstay Fabry treatment is enzyme replacement therapy (ERT), which temporarily provides the body with a functional version of the alpha-Gal A enzyme. Because the body cannot produce the enzyme on its own and the infused enzyme typically remains in circulation for only a few hours, patients require lifelong ERT infusions.
Given as a single infusion into the bloodstream, isaralgagene civaparvovec is designed to deliver a healthy copy of the gene encoding alpha-GalA to liver cells, restoring the body’s ability to produce a functional version of the enzyme. This is expected to ease Fabry symptoms and slow or stop disease progression.
The BLA submission was supported by data from the Phase 1/2 STAAR trial (NCT04046224). The trial evaluated the one-time gene therapy in 33 adults with Fabry disease who were followed for one year, after which they could enter a five-year extension study (NCT05039866). Eighteen of them had been receiving ERT before gene therapy, while 15 had not.
In line with earlier findings, data from the STAAR trial presented at a recent scientific conference showed that, at one year after isaralgagene civaparvovec treatment, the average slope of estimated glomerular filtration rate (eGFR) remained positive. eGFR is a standard measure of how well the kidneys filter blood, and a positive slope indicates that kidney function improved following treatment. A similar pattern was observed in 19 patients with available data two years after gene therapy.Â
These findings contrast with what is typically seen in untreated people with Fabry, where the rate of change in eGFR is usually negative, reflecting the progressive loss of kidney function as the disease advances and organ damage accumulates. Available treatments such as ERT can help slow this decline, but most patients still experience a negative eGFR rate, indicating worsening kidney function over time.
The FDA has agreed that the one-year eGFR slope from the STAAR trial may serve as the primary endpoint supporting the therapy’s application for accelerated approval.
Measures of heart health also remained stable over the two years following treatment with isaralgagene civaparvovec. The gene therapy led to sustained increases in alpha-Gal A enzyme activity, and as of the latest follow-up all 18 patients who had entered the study while on ERT were able to discontinue it.
The therapy was generally well tolerated. Reported side effects were mostly mild to moderate, with the most common including fever, headache, COVID-19, fatigue, and the common cold.
