Sangamo hits milestone toward accelerated approval for ST-920
Developer: All patients given Fabry gene therapy in trial reach 1-year mark
All patients who have so far received the gene therapy candidate ST-920 (isaralgagene civaparvovec) — being developed by Sangamo Therapeutics for Fabry disease — in a Phase 1/2 clinical trial have reached the one-year mark required by the U.S. Food and Drug Administration (FDA) before the company can take the next step toward accelerated approval.
That’s according to a new update from Sangamo, which announced in a company press release that a “pivotal data readout” is expected by the end of June.
The FDA had already said that data from the ongoing Phase 1/2 STAAR trial (NCT04046224) could serve as the main evidence for accelerated approval, eliminating the need for additional clinical testing to confirm the benefit of ST-920 for Faby patients. This could shorten the time it will take for the therapy to enter the market.
In a Type B meeting with the FDA, Sangamo also received clear guidance on how to complete the next steps for manufacturing and quality — known as chemistry, manufacturing, and control plans — keeping the company on track to file a biologics license application (BLA) requesting the therapy’s approval in early 2026. If all goes as expected, the gene therapy could become available in the second half of 2026, per Sangamo.
“We have a clear regulatory pathway to a potential approval decision for ST-920 and we continue to advance BLA preparation activities,” said Nathalie Dubois-Stringfellow, PhD, Sangamo’s chief development officer.
New data analysis shows continued positive results with ST-920
The company said a preliminary analysis of one-year data showed continued positive results with the experimental gene therapy.
Building on early data showing that ST-920 continues to maintain a positive slope in estimated glomerular filtration rate (eGFR) — an indicator that kidney function is improving over time — Sangamo is now planning to file the BLA at the start of next year.
“Following last year’s alignment with the FDA on an accelerated approval regulatory pathway for ST-920, we are excited to have now gathered the one-year mean eGFR slope data that will serve as the primary efficacy endpoint for our planned BLA,” Dubois-Stringfellow said.
Meanwhile, discussions with European regulators are underway for a similar application, according to the company.
Following last year’s alignment with the FDA on an accelerated approval regulatory pathway for ST-920, we are excited to have now gathered the one-year … data that will serve as the primary efficacy endpoint for our planned BLA [biologics license application].
Fabry disease is caused by mutations in the GLA gene that result in little or no activity of alpha-Gal A, an enzyme responsible for breaking down fatty molecules. Without this enzyme, these fatty molecules accumulate to toxic levels in cells, damaging the kidneys and other organs in the body.
Delivered as a single infusion into the bloodstream, ST-920 is designed to deliver a healthy version of the GLA gene to cells in the liver. This enables liver cells to produce a functional version of alpha-Gal A, which is expected to break down and clear the toxic fatty molecules, thereby easing Fabry disease symptoms.
The STAAR study is testing how safe and well tolerated ST-920 is in more than 30 men and women with a diagnosis of Fabry disease. Patients are being followed for 52 weeks, or one year. Then, they may enter an extension study (NCT05039866) to continue being monitored for up to a total of five years following dosing. The longest-participating patient may have completed more than four years of follow-up.
1-year trial data needed for accelerated approval of gene therapy
In line with an earlier analysis, more recent data presented at a scientific meeting showed that ST-920 remains well tolerated. Side effects were mostly mild to moderate, the most common being fever, headache, COVID-19, cold-like symptoms, fatigue, and nausea.
As of mid-September 2024, all patients treated with ST-920 showed a sustained increase in alpha-Gal A activity in the blood to levels above the normal average, along with reduced levels of lyso-Gb3, a fatty molecule normally broken down by the enzyme.
All 18 patients who had started the study on enzyme replacement therapy (ERT), which works by temporarily providing the body with a functional alpha-Gal A, were able to stop it. Their alpha-Gal A activity and lyso-Gb3 remained at normal or above-normal levels despite remaining off ERT.
Among the 23 patients who by that time had been followed for at least one year, the average eGFR slope remained positive, meaning that their kidney function was stable or improving. These patients also experienced improvements in quality of life and relief of other symptoms of Fabry disease.
The FDA has granted Sangamo fast track designation to ST-920 for Fabry disease, which has enabled the company to have more frequent interactions with U.S. regulators throughout the clinical development of its gene therapy. ST-920 has also been designated an orphan drug in the U.S. and the European Union, and a regenerative medicine advanced therapy in the U.S.
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