Fabry disease gene therapy study data enough for FDA submission
Findings could serve as main evidence for ST-920's accelerated approval
Data from an ongoing Phase 1/2 clinical study of ST-920 (isaralgagene civaparvovec), an investigational gene therapy for Fabry disease, could serve as the main evidence for its accelerated approval by the U.S. Food and Drug Administration (FDA), eliminating the need for an additional registrational study to confirm its clinical benefit.
The full dataset from STAAR (NCT04046224), which is needed for the accelerated approval, will be ready in the first half of 2025, enabling developer Sangamo Therapeutics to seek a biologics license application by the second half of the year, three years earlier than expected. This could shorten the time for ST-920 to enter the market.
In an earlier meeting, the FDA agreed a well-controlled registrational study, along with existing data, could be sufficient as the basis for ST-920’s approval, but it’s now providing an alternative clear regulatory pathway to accelerated approval, which grants a go-ahead based on a surrogate marker that’s thought to predict clinical benefit.
“I strongly believe in the potential for ST-920 to alleviate many manifestations of Fabry disease and am delighted to have a clear regulatory pathway that could bring this treatment to patients significantly sooner than originally anticipated,” Sandy Macrae, PhD, Sangamo’s CEO, said in a company press release.
Fabry disease is caused by mutations in the GLA gene, which provides instructions for producing alpha-Gal A, an enzyme that works to break down fatty molecules. When the enzyme is faulty, the molecules build up to toxic levels in cells, leading to progressive organ damage, particularly affecting the heart, kidneys, and nervous system, and resulting in a range of symptoms.
Infused as a single dose into the bloodstream, ST-920 is designed to deliver a healthy version of GLA to liver cells so they can produce a working alpha-Gal A enzyme on their own to support the breakdown of fatty molecules like Gb3 and help alleviate symptoms.
Testing ST-920 in Fabry disease patients
STAAR is testing the safety and tolerability of ST-920 in 33 men and women with a diagnosis of Fabry disease. The patients are being followed for 52 weeks, after which they can enter a five-year extension (NCT05039866). The patient who’s been in the study the longest recently completed four years of follow-up.
Interim data showed ST-920 was well tolerated, with the most common side effects being fever, headache, viral infection, fatigue, and cold-like symptoms. All the participants showed a sustained increase in alpha-Gal A enzyme levels and saw their symptoms become less severe.
All 18 patients who started the study on enzyme replacement therapy (ERT), which temporarily provides a working version of alpha-Gal A, were able to stop it. The patients’ alpha-Gal A levels remained at normal or above-normal despite being off ERT.
Nearly all Fabry patients have kidney problems, such as passing protein into the urine or a reduced glomerular filtration rate (eGFR), an indicator that the kidneys aren’t filtering blood as well as they should, that sometimes leads to kidney failure. In the 18 patients who had more than a year of follow-up, ST-920 resulted in significant improvements in eGFR, suggesting better kidney function. Based on these data, the FDA agreed that the eGFR slope, a measure of how kidney function changes over time, at 52 weeks could serve as a primary basis for approval. The FDA also suggested calculating the eGFR slope at 104 weeks to confirm long-term benefit.
Sangamo was awarded fast track status for ST-920 last year, allowing the company to begin engaging with the FDA more frequently. ST-920 also has orphan drug and regenerative medicine advanced therapy designations in the U.S., and orphan medicinal product designation and priority medicines eligibility in the European Union.
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