Sangamo Therapeutics Aligns With FDA for Accelerated ST-920 Approval, BLA Submission in 2025

Sangamo Therapeutics, Inc., a company specializing in genomic medicine, has announced a significant advancement in its gene therapy product, isaralgagene civaparvovec (ST-920), designed to treat Fabry disease. Following a successful meeting with the U.S. Food and Drug Administration (FDA), Sangamo has been granted a clear path towards Accelerated Approval for ST-920, using data from their ongoing Phase 1/2 STAAR study. This decision by the FDA eliminates the need for an additional registrational study, potentially bringing forward the approval timeline by approximately three years.

The FDA's decision was based on the analysis of data from the Phase 1/2 STAAR study, which demonstrated promising safety and effectiveness, particularly in improving kidney function in patients with Fabry disease. The FDA has agreed that the slope of the estimated glomerular filtration rate (eGFR) at 52 weeks can serve as the primary basis for approval under the Accelerated Approval pathway. The complete dataset required to support this pathway is expected to be available in the first half of 2025. Consequently, Sangamo anticipates submitting a Biologics License Application (BLA) in the second half of 2025.

Fabry disease is a genetic disorder impacting the GLA gene, leading to a deficiency in the enzyme alpha-galactosidase A (α-Gal A). This deficiency results in the accumulation of globotriaosylceramide (Gb3) in cells, causing damage to vital organs such as the kidneys, heart, and nervous system. Symptoms of Fabry disease include kidney disease, heart failure, and neuropathic pain, among others. Without effective treatment, patients with Fabry disease often face a diminished quality of life and reduced life expectancy.

Sangamo's Phase 1/2 STAAR study is a global, open-label, single-dose, dose-ranging, multicenter clinical trial, aimed at evaluating the safety and tolerability of isaralgagene civaparvovec. The study included both male and female patients who were either on Enzyme Replacement Therapy (ERT), pseudo-naïve to ERT (off ERT for six or more months), or completely ERT-naïve. The treatment involves a one-time infusion of the gene therapy without the need for preconditioning.

Throughout the trial, significant improvements were observed in patients' eGFR levels, indicating better kidney function. Renal complications are common in Fabry disease, often leading to end-stage renal disease and premature death. The encouraging results from the STAAR study prompted the FDA to consider eGFR slope as a viable intermediate clinical endpoint for Accelerated Approval, with a longer-term view of assessing eGFR slope at 104 weeks to verify clinical benefit.

By April 2024, dosing in the Phase 1/2 STAAR study had been completed, with a total of 33 patients treated. The longest-treated patient had reached four years of follow-up, and all 18 patients who began the study on ERT had successfully discontinued ERT by September 2024, remaining off ERT as of the latest update.

Sangamo is actively preparing for the BLA submission for isaralgagene civaparvovec, while also exploring potential collaboration opportunities to advance the development and commercialization of the treatment. The company remains committed to addressing the significant unmet medical needs of patients with Fabry disease and is optimistic about the impact that ST-920 could have on improving patient outcomes.

The progress made by Sangamo in navigating the regulatory pathway with the FDA highlights the potential of gene therapy to transform treatment paradigms for genetic disorders such as Fabry disease. With continued advancements and collaboration, Sangamo aims to bring this innovative therapy to patients sooner than initially anticipated, offering hope for improved management and quality of life for those affected by this debilitating condition.