Sangamo's Gene Therapy Shows Sustained Benefits in Fabry Disease Patients with Improved Kidney Function
核心洞察
Updated Phase 1/2 STAAR (搜索) study data demonstrates sustained α-Gal A enzyme activity for up to 47 months, with all 18 ERT-dependent patients successfully discontinuing enzyme replacement therapy (搜索).
Patients showed significant kidney function improvements with a positive mean annualized eGFR slope of 3.061 mL/min/1.73m2/year, indicating potential disease-modifying effects.
Sangamo plans BLA submission in second half of 2025 following FDA's agreement to consider Accelerated Approval pathway based on 52-week eGFR data.
The latest data from Sangamo Therapeutics' Phase 1/2 STAAR (搜索) study reveals promising outcomes for isaralgagene civaparvovec (ST-920), a novel gene therapy for Fabry disease (搜索). The updated results, with a data cutoff date of September 12, 2024, demonstrate sustained therapeutic benefits and favorable safety profile in treated patients.
Sustained Therapeutic Effect and ERT Independence
The gene therapy continues to show durable enzyme expression, with the longest-treated patient maintaining elevated α-Gal A activity for nearly four years (47 months). Notably, all 18 patients previously dependent on enzyme replacement therapy (搜索) (ERT) have successfully discontinued their treatment and remain ERT-free, with stable plasma lyso-Gb3 levels for up to 33 months post-withdrawal.
Significant Improvements in Kidney Function
Among the 23 patients with at least 12 months of follow-up, researchers observed a positive mean annualized eGFR slope of 3.061 mL/min/1.73m2/year (95% CI: 0.863, 5.258). This improvement in kidney function represents a crucial advancement, as renal decline is a major predictor of morbidity and mortality in Fabry disease (搜索) patients.
Quality of Life and Disease Severity Outcomes
The study documented substantial improvements in patient quality of life measures. The SF-36 General Health score showed a mean increase of 10.6 points (p=0.0020), significantly exceeding the minimal clinically important difference of 3-5 points. Fifteen patients demonstrated improvements in their Fabry Outcome Survey adaptation of the Mainz Severity Score Index (FOS-MSSI).
Safety Profile and Tolerability
Isaralgagene civaparvovec maintained its favorable safety profile, with most adverse events being mild to moderate (grade 1-2). Importantly, no liver function test elevations requiring steroid intervention were reported, and no adverse events led to study discontinuation.
Regulatory Path Forward
Professor Derralynn Hughes of the Royal Free London NHS Foundation Trust, a study investigator, commented, "These updated data from the Phase 1/2 STAAR (搜索) study are highly encouraging, particularly the positive mean eGFR slope observed in patients with at least one year of follow-up, indicating improvements in renal function."
Following productive discussions with the FDA, Sangamo has secured a clear pathway to Accelerated Approval using the 52-week eGFR slope data as an intermediate clinical endpoint. The company expects to have complete 52-week eGFR slope data in the first half of 2025, with plans to submit a Biologics License Application (BLA) in the second half of 2025.
Immunological Response
The therapy has shown promising results in addressing pre-existing antibodies against α-Gal A. Of ten patients who had measurable antibody titers at baseline, nine experienced significant decreases in total or neutralizing antibodies, with complete elimination in seven cases following ST-920 treatment.