Sangamo’s Gene Therapy Promising for Fabry Disease


Updated data from the STAAR clinical trial were presented at the SSIEM Annual Meeting.

Isaralgagene civaparvovec (ST-920; Sangamo Therapeutics) has been well-tolerated and restored production of α-galactosidase A (α-Gal A) in people with Fabry disease, according to updated data from the phase 1/2 STAAR clinical trial (NCT04046224).

These data, collected from the first 6 patients dosed in 3 cohorts up until the February 14, 2022, cutoff date, were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Meeting, August 31, 2022, in Freiburg, Germany. Five patients had follow-up for up to 15 months while the sixth patient had a 2-week follow-up as of the cutoff date.

“These updated preliminary results continue to demonstrate the potential of isaralgagenecivaparvovec gene therapy to safely address the most challenging symptoms of Fabry disease,” study investigator Jaya Ganesh, MD, Division of Medical Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, said in a statement. “I am excited to see whether these encouraging trends continue into the next dose cohort and beyond, as we progress this potential treatment for a very challenging illness.”

ST-920 has continued to demonstrate a tolerable safety profile with no treatment-related adverse events (AEs) above Grade 1. Sustained α-Gal A activity was observed in all 6 patients, from 2 weeks after dosing to the longest follow-up of 15 months after dosing. Patients ranged from 22 to 48 years of age. The first 5 patients had nearly 3-fold to nearly 17-fold above mean normal levels while the sixth patient exhibited a normal range of α-Gal A activity 2 weeks after dosing. One patient has discontinued enzyme replacement therapy (ERT) and continues to show elevated activity levels 12 weeks post-withdrawal.

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Three patients have also reported symptom improvement, including in the ability to sweat. Patients with Fabry cardiomyopathy have not experienced progression. One patient, with the most significant elevation in plasma globotriaosylsphingosine (lyso-Gb3) pre-treatment, experienced a significant reduction of around 40% from baseline within 10 weeks after treatment. This improvement was sustained through week 48 after treatment. Another patient had a moderate increase in lyso-Gb3 levels after withdrawing ERT. Lyso-Gb3 levels were sustained in the other 4 patients with lower baseline levels.

“We are excited by the strong progress of our wholly owned Fabry program, which we believe places us in a leading position to offer patients a compelling potential therapy for their underlying disease,” Nathalie Dubois-Stringfellow, PhD, senior vice president and chief development officer, Sangamo, added to the statement. “We look forward to sharing an update on the additional patients dosed and continue to actively prepare for a potential Phase 3 trial.”

The open-label, dose-escalation, multicenter study is enrolling patients with Fabry regardless of ERT status for a single infusion of ST-920. The therapy has been granted orphan drug designation from the FDA and orphan medicinal product designation from the EMA.

Five more patients have been dosed in the STAAR study since the cutoff date and the study has advanced to its dose escalation phase. There are currently 2 patients each in cohorts 1 (0.5e13 vg/kg) and 2 (1e13 vg/kg), 3 in cohort 3 (3e13 vg/kg), 2 in cohort 4 (3e13 vg/kg), and 2 in the expansion phase at the 5e13 vg/kg dose level. Another 4 patients have discontinued ERT and multiple additional patients, both male and female, are in screening. More updates from STAAR will be announced in the second half of 2022 and Sangamo is currently planning for a possible phase 3 trial.

Sangamo Therapeutics announces updated preliminary phase 1/2 data in Fabry disease clinical study showing continued tolerability and sustained elevated α-gal A enzyme activity in five longest treated patients. News release. Sangamo Therapeutics. August 30, 2022.
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