Sangamo Therapeutics Advances Fabry Disease Gene Therapy Toward FDA Submission Following Positive Clinical Data
核心洞察
Sangamo's isaralgagene civaparvovec demonstrated positive kidney function outcomes in Fabry disease (搜索) patients, with a mean annualized eGFR (搜索) slope of 1.965 mL/min/1.73m²/year at 52 weeks across 32 dosed patients.
The FDA reiterated its agreement to use eGFR (搜索) slope as an endpoint for accelerated approval pathway, positioning the company for a potential BLA submission in Q1 2026.
All 18 patients who began the study on enzyme replacement therapy were successfully withdrawn from ERT and remained off treatment, demonstrating the therapy's potential as a durable alternative.
Sangamo Therapeutics reported significant progress in its Fabry disease (搜索) gene therapy program, presenting detailed clinical data from the registrational Phase 1/2 STAAR study that positions isaralgagene civaparvovec (ST-920) for potential regulatory approval. The company held a productive meeting with the FDA in October, where regulators reiterated their October 2024 agreement to use estimated glomerular filtration rate (eGFR (搜索)) slope as an endpoint to support an accelerated approval pathway.
Promising Kidney Function Outcomes
The STAAR study demonstrated encouraging kidney function preservation across 32 dosed patients. A positive mean annualized eGFR (搜索) slope of 1.965 mL/min/1.73m²/year (95% confidence interval: -0.153, 4.083) was observed at 52 weeks. For the 19 patients who reached 104 weeks of follow-up, the mean annualized eGFR slope remained positive at 1.747 mL/min/1.73m²/year (95% CI: -0.106, 3.601).
The consistency of these results across various patient subgroups, including gender, baseline enzyme replacement therapy (ERT) status, Fabry disease (搜索) type, and baseline eGFR (搜索), suggests broad applicability of the treatment's benefits across the Fabry patient population.
Multi-Organ Benefits and Treatment Durability
Beyond kidney function, the study revealed stable cardiac function parameters, including left ventricular mass, left ventricular mass index, and myocardial global longitudinal strain that remained stable over at least one year. Durability of effect was demonstrated through elevated expression of alpha-galactosidase A (搜索) (α-Gal A) activity maintained for up to 4.5 years in the longest treated patient.
A particularly notable finding was that all 18 patients who began the study on ERT were successfully withdrawn from ERT and remained off treatment as of the data cutoff date. Plasma lyso-Gb3 levels in these patients remained generally stable following ERT withdrawal, indicating the gene therapy's ability to replace conventional treatment.
Quality of Life Improvements
Patients experienced statistically and clinically significant improvements in quality of life measures. The short form-36 (SF-36) quality of life scores showed significant improvements, alongside statistically significant improvements in the gastrointestinal symptom rating scale (GSRS) compared to baseline. Disease severity improvements were reported in the Fabry Outcome Survey adaptation of the Mainz Severity Score Index, with 22 patients showing improvements in their total score at 12 months.
Safety Profile and Regulatory Path
Isaralgagene civaparvovec demonstrated a favorable safety and tolerability profile without requiring preconditioning. The treatment also showed benefits in reducing antibody burden, with nine of 10 patients who had measurable antibody titers against α-Gal A at baseline experiencing marked decreases, and eight becoming undetectable following treatment.
Sangamo is preparing for an anticipated Biologics License Application (BLA) submission as early as the first quarter of 2026, while continuing business development discussions for a Fabry commercialization agreement.
Expanding Neurology Pipeline
The company also advanced its neurology pipeline with the initiation of patient enrollment in the Phase 1/2 STAND study evaluating ST-503 for chronic neuropathic pain (搜索). This investigational epigenetic regulator targets intractable pain due to small fiber neuropathy (搜索), with the first patient expected to be dosed in the coming months.
For prion disease (搜索), Sangamo continues advancing ST-506 (搜索) toward clinical trials, with productive interactions with the UK's Medicines and Healthcare products Regulatory Agency (MHRA). Updated preclinical data presented at the Prion 2025 Conference demonstrated profound survival extension in disease mouse models and widespread brain delivery in nonhuman primates. A Clinical Trial Application submission for ST-506 is expected as early as mid-2026.
Financial Position and Outlook
The company reported a consolidated net loss of $34.9 million for the third quarter of 2025, with cash and cash equivalents of $29.6 million as of September 30, 2025. Based on current operating plans, including recent funding from Pfizer and proceeds from stock sales, Sangamo believes its resources will be sufficient to fund operations into the first quarter of 2026.
CEO Sandy Macrae emphasized the significance of these developments, stating that the detailed clinical data from the STAAR study and recent FDA meeting "marked important steps forward on the path to an anticipated regulatory submission for this program."