Sangamo announces topline results from STAAR study

Sangamo (SGMO) announced topline results from the registrational Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned investigational gene therapy for the treatment of adults with Fabry disease. Following a single dose of isaralgagene civoparvovec, a positive mean annualized eGFR slope of 1.965 mL/min/1.73m2/year at 52-weeks was observed across all 32 dosed patients in the study, which the FDA has agreed will serve as an intermediate clinical endpoint under the Accelerated Approval pathway. Furthermore, a mean annualized eGFR slope of 1.747 mL/min/1.73m2/year was observed for the 19 patients who have achieved 104-weeks of follow-up. As recommended by the FDA, Sangamo plans to compare the annualized mean eGFR slope of isaralgagene civaparvovec with approved treatments for Fabry disease by performing a meta-analysis of published studies. According to observational studies, estimated mean annualized eGFR slopes for other marketed treatment options range from -2.2 to -0.4 mL/min/1.73m2/year for treatments such as Replagal, Fabrazyme and Galafold. The company believes these data support the potential for isaralgagene civaparvovec as a one-time, durable treatment for Fabry disease that can improve patient outcomes and will form the basis for an anticipated BLA submission under the Accelerated Approval pathway as early as the first quarter of 2026. The STAAR study enrolled male and female patients who were either on enzyme replacement therapy, were ERT pseudo-naive, or were ERT-naive. The median age of patients enrolled in the study was 42, with a median duration of follow-up of 24 months and the longest treated patient having achieved 4.5 years of follow-up. Key secondary endpoints in the study were also positive. Elevated expression of alpha-galactosidase A activity was maintained for up to 4.5 years for the longest treated patient. All 18 patients who began the study on ERT have been withdrawn from ERT and all remain off ERT as of today. Plasma lyso-Gb3 levels in these patients remained generally stable following ERT withdrawal. A stabilization in cardiac endpoints was also observed. Patients demonstrated a range of other clinical benefits, including improvements in disease severity reported in the Fabry Outcome Survey adaptation of the Mainz Severity Score Index age-adjusted score and statistically and clinically significant improvements in the short form-36 quality of life scores, including role-physical +14.8, vitality +9.6, bodily pain +9.0, social functioning +7.8, general health +7.4, and physical component scores +4.2, at week 52 compared to baseline. Statistically significant improvements in the gastrointestinal symptoms rating scale compared to baseline were also observed. Furthermore, following a single administration of isaralgagene civaparvovec, additional clinical benefits were observed in some patients, such as the reduction or elimination in pain medication usage and the resumption of sweating, that has enabled these patients to perform physical tasks and exercise. Isaralgagene civaparvovec demonstrated a favorable safety and tolerability profile in the study, without the requirement for preconditioning. The majority of adverse events were grade 1-2 in nature. The most common treatment-emergent adverse events were pyrexia, COVID-19, headache and nasopharyngitis. All TEAEs resolved in response to clinical management and there were no safety-related study discontinuations.