Fabry disease treatment ST-920 improves kidney function: Data
Measures improved in year following single dose, top-line data show
Fabry disease patients showed improvements in kidney function in the year following a single dose of gene therapy ST-920 (isaralgagene civaparvovec), and reductions in disease severity were seen at a median of two years after treatment.
That’s according to top-line data from the Phase 1/2 STAAR trial (NCT04046224). The findings were announced by Sangamo Therapeutics, the company developing ST-920 and sponsoring the trial.
“These data demonstrate the potential for a single dose of ST-920 to provide meaningful clinical benefits above current standards of care and to treat the underlying [disease biology] of Fabry disease,” Nathalie Dubois-Stringfellow, PhD, Sangamo’s chief development officer, said in a company press release. “We want to thank the patients and investigators who participated in this study and look forward to sharing these data with health authorities.”
Based on the positive findings, Sangamo plans to ask the U.S. Food and Drug Administration (FDA) to grant accelerated approval to ST-920. Accelerated approval is a form of conditional approval in which the FDA allows a therapy to be brought to market while requiring the treatment’s developer to conduct additional tests to prove it gives clinical benefits to patients.
The FDA previously indicated that data from the STAAR study could serve as a basis for accelerated approval of ST-920, and Sangamo said it expects to have an application submitted as soon as early 2026.
Fabry disease treatment aims to deliver healthy version of gene
Fabry disease is caused by mutations in the GLA gene, which provides instructions to make an enzyme called alpha-Gal A that’s needed to break down certain fatty molecules. Deficiency of this enzyme leads these fatty molecules to build to toxic levels in cells, causing organ damage that drives Fabry symptoms. Kidney damage is a common manifestation of Fabry disease.
ST-920 is designed to deliver a healthy version of the GLA gene to cells in the liver, facilitating production of a healthy alpha-Gal A enzyme that can break down toxic fatty molecules. The gene therapy is administered by a one-time infusion into the bloodstream.
In the STAAR study, 32 people with Fabry disease were treated with ST-920. The study enrolled men and women, some who had previously been on enzyme replacement therapy (ERT) and some who had not. The median age of the study participants was 42. Most have now been followed for at least two years after ST-920 treatment, with some followed for more than four years since gene therapy.
Kidney function in STAAR was tracked with a standard measure called estimated glomerular filtration rate (eGFR), which assesses how efficiently the kidneys are able to filter blood. eGFR is measured in a unit called milliliters per minute per 1.73 square meters (mL/min/1.73m2).
Findings from STAAR showed that, in the year after ST-920 treatment, eGFR tended to increase (improve) at a rate of 1.965 mL/min/1.73m2/year. Among 19 patients who’ve been followed for two years, eGFR tended to increase over the duration of follow-up at a rate of 1.747 mL/min/1.73m2/year.
According to Sangamo, these improvements in eGFR over time represent a marked contrast with current Fabry treatments, where eGFR tends to decrease (worsen) over time, the company said.
Higher levels of alpha-Gal A enzyme activity were seen for up to 4.5 years in the patient who received the treatment earliest. All 18 patients who were originally on ERT have stopped it. Their blood levels of lyso-Gb3, a marker of Fabry disease, stayed mostly stable after stopping ERT. Heart function also remained stable during this time.
In addition to the increase in eGFR, patients in the STAAR study also experienced improvements in scores on the Fabry Outcome Survey adaptation of the Mainz Severity Score Index (FOS-MSSI), a measure of overall disease severity, and in the gastrointestinal symptoms rating scale (GSRS), which measures the severity of digestive symptoms. Scores on the short form-36 (SF-36), a measure of overall life quality, also tended to improve following ST-920 treatment, according to Sangamo. The company said some participants also reported less need for pain medication and more normalized sweating.
“We are thrilled to see these compelling topline STAAR study results, including the positive mean annualized eGFR slope at both 52 and 104 weeks, alongside notable improvements in a range of secondary endpoints,” Dubois-Stringfellow said.
ST-920 was generally tolerated well in the study, according to Sangamo. Most safety issues reported in the study were not serious. The most common safety issues documented during the trial were fever, COVID-19, the common cold, and headache. All safety issues that occurred during the trial were resolved with standard medical management.
Detailed results from STAAR will be presented at an “upcoming medical meeting,” Sangamo said.
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