Sangamo Therapeutics, Inc. announced updated preliminary results from the Phase 1/2 STAAR clinical study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned gene therapy product candidate for the treatment of Fabry disease. These latest data show that, as of the February 14, 2022 cutoff date, the investigational treatment continued to be generally well tolerated, with no treatment-related adverse events above Grade 1 (mild). The five longest treated patients continued to exhibit elevated alpha-galactosidase A (a-Gal A) activity, sustained up to 15 months as of the last date of measurement.

The sixth patient exhibited elevated a-Gal A activity to within normal range at two weeks post dosing. These updated data will be presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting on August 31, 2022, from 6:45pm-8:15pm Central European Time (Ref: SSIEM22-2517). As of the cutoff date, the first five patients treated, across three dose cohorts (0.5e13 vg/kg, 1e13 vg/kg and 3e13 vg/kg), sustained elevated a-Gal A activity ranging from nearly 3-fold to nearly 17-fold above mean normal at the last date of measurement.

Cohort 1, Patient 1 [on ERT at the cutoff date]: a-Gal A activity measured at ERT trough was 12.4-fold above mean normal at Month 15. Cohort 1, Patient 2 [not on ERT]: a-Gal A activity was 2.7-fold above mean normal at Month 15. Cohort 2, Patient 1 [not on ERT]: a-Gal A activity was 3.5-fold above mean normal at Week 48.

Cohort 2, Patient 2 [began the study on ERT and was subsequently withdrawn from ERT at week 24]: a-Gal A activity was 10.3-fold above mean normal at Week 36. This represents a sustained a-Gal A expression compared with the 10-fold above mean normal levels previously exhibited as of November 9, 2021, with a-Gal A expression one week post ERT withdrawal. Cohort 3, Patient 1 [on ERT at the cutoff date]: a-Gal A activity measured at ERT trough was 16.7-fold above mean normal at Week 16.

Cohort 3, Patient 2 [on ERT at the cutoff date]: a-Gal A activity measured at ERT trough increased to within normal range at Week 2. As of the cutoff date, isaralgagene civaparvovec was generally well tolerated across three dose cohorts in the six treated patients, with no treatment-related adverse events higher than Grade 1 (mild) and no treatment-related serious adverse events. No patients experienced liver enzyme elevations requiring steroid treatment, and no prophylactic steroid treatments had been used. Three patients have anecdotally reported improvements in their symptoms, including improvements in the ability to sweat, a primary and common Fabry disease symptom.

No progression of Fabry cardiomyopathy was observed in those patients who presented with signs of cardiomyopathy on cardiac MRI at baseline. The first patient in Cohort 2 with the most significant elevation in plasma globotriaosylsphingosine (lyso-Gb3) pre-treatment, showed a significant reduction of approximately 40% from baseline levels of plasma lyso-Gb3 within 10 weeks after dosing which was sustained through Week 48. The second patient in Cohort 2 demonstrated a moderate increase in lyso-Gb3 levels since the withdrawal of ERT.

The other four patients with lower baseline levels of lyso-Gb3 sustained steady levels through the cutoff date. Since the cutoff date, an additional five patients have been dosed in the Phase 1/2 STAAR study, resulting in a total of eleven patients dosed to date – one additional patient in Cohort 3, two patients in Cohort 4 at the 5e13 vg/kg dose level and the first two patients in the expansion phase at the 5e13 vg/kg dose level. There are multiple additional patients in screening, including both male and female candidates.

Out of the five treated patients in the dose escalation phase who began the STAAR study on ERT, an additional four have been withdrawn from ERT since the cutoff date, completing ERT withdrawal for all patients in this dose escalation phase of the study. Sangamo expects to provide additional results from the STAAR study in the second half of 2022 and is currently planning for a potential Phase 3 clinical trial.