Gene Therapy Well-Tolerated in Fabry Disease


Primary efficacy data released by Sangamo Therapeutics showed that above normal α-Gal A activity was maintained for up to a year after treatment.

Isaralgagene civaparvovec (ST-920; Sangamo Therapeutics) has shown efficacy in treating Fabry disease, according to new data from the phase 1/2 STAAR clinical study (NCT04046224).

Sangamo Therapeutics announced the updated data, which showed that the gene therapy was generally well-tolerated in patients with Fabry disease. In terms of efficacy, all 4 patients in the first 2 cohorts maintained above normal α-Gal A activity for up to 1 year since treatment with isaralgagene civaparvovec.

“There is significant unmet need in Fabry disease, a progressive and challenging condition that is currently treated with frequent burdensome infusions that do not adequately address the underlying disease,” Rob Schott, MD, MPH, FACC, head, development, Sangamo, said in a statement.

Data were available from 4 patients dosed in the 0.5e13 vg/kg and 1e13 vg/kg cohorts. As of September 17, 2021, α-Gal A activity was 2-fold to 15-fold above mean normal. Two patients were being treated with enzyme replacement therapy (ERT) at the start of the study; 1 has discontinued treatment and the other is also planning to discontinue ERT, based on their α-Gal A activity stability.

READ MORE: Gene Therapies Show Efficacy in Fabry Disease, Choroideremia

Prior to treatment, 1 patient had a significant elevation in plasma lyso-Gb3, which significantly reduced by around 40% from baseline to 10 weeks post-dosing. This reduction was maintained through 32 weeks post-treatment. Lyso-Gb3 levels were steady through the cutoff date in patients with low baseline levels.

No over grade 1 or serious treatment-related adverse events (AEs) have been observed as of the cutoff date. No liver enzyme elevations requiring steroid treatment were observed. 

“We are encouraged by these early yet promising results, particularly that the first three treated patients dosed all reported improvements in their ability to sweat, which is noteworthy as this limits a person’s capability to tolerate strenuous tasks and exercise. As we continue with this study, we hope to further understand the potential treatment effect over the longer-term and in more patients, while we initiate plans for a Phase 3 trial,” Schott added.

The STAAR study is an open-label, single-dose, dose-ranging, multicenter study evaluating the safety and tolerability of 1 infusion of isaralgagene civaparvovec. The gene therapy has been granted orphan drug designation by the FDA and orphan medicinal product designation from the EMA.

A fifth patient, for which data was not available at the cutoff date, has also been dosed in a third dose cohort (3e13vg/kg). A sixth patient is currently being screened for the third dose cohort. Sangamo expects to present updated data at future scientific meetings throughout 2022. The company is planning a phase 3 trial of isaralgagene civaparvovec based on the positive data seen in the phase 1/2 study.

Sangamo is also developing the gene therapy giroctocogene fitelparvovec for hemophilia A, which is in phase 3 studies, and the cell therapies TX200 for renal transplant and SAR445136 for sickle cell disease, both of which are in phase 1/2 studies. Sangamo will present updated follow-up data from the phase 1/2 Alta study (NCT03061201) of giroctocogene fitelparvovec in patients with severe hemophilia at the 63rd American Society of Hematology Annual Meeting, December 11-14, 2021.

Sangamo Therapeutics announces preliminary phase 1/2 data showing tolerability and sustained elevated α-Gal A enzyme activity in patients with Fabry Disease. News release. Sangamo Therapeutics. November 4, 2021.
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