Patients With Fabry Disease Withdrawn From ERT After Isaralgagene Civaparvovec Treatment


All 5 patients on ERT at study start have since been able to withdraw after gene therapy treatment.

Patients with Fabry disease treated with isaralgagene civaparvovec(ST-920; Sangamo Therapeutics) tolerated the therapy well and experienced significant alpha-galactosidase A (α-Gal A) elevations, according to updated data from the phase 1/2 STAAR clinical trial (NCT04046224).

These data were presented by investigator Patrick Deegan, MD, Cambridge University Hospitals NHS Foundation Trust, at the 29th Congress of the European Society of Gene & Cell Therapy (ESGCT) 2022, taking place October 11-14 in Edinburgh, Scotland.

“I’m encouraged by these results, showing isaralgagene civaparvovec gene therapy has reassuring safety data to date, with no requirement for corticosteroid therapy,” Deegan said in a statement. “ST-920 has the potential to provide an alternative to enzyme replacement therapy for patients with Fabry disease. I look forward to seeing additional data as we continue to progress this important program.”

As of the July 21, 2022, cutoff date, all 9 patients had exhibited elevated α-Gal A activity for up to 23 months longest follow-up. These patients were enrolled across 4 dose cohorts of 0.5e13 vg/kg, 1e13 vg/kg, 3e13 vg/kg and 5e13 vg/kg and α-Gal A activity has ranged from nearly 2-fold to 30-fold of mean normal.

READ MORE: Fabry Disease Gene Therapy Clinical Trial Moves Onto Dosing Second Cohort

Specifically, patients in cohort 1 had 30.4-fold and 1.9-fold of mean normal; patients in cohort 2 had 3.7- and 7.9-fold mean normal; patients in cohort 3 had 14.7- and 4.8-fold mean normal; and patients in cohort 4 had 5.4- and 9.0-fold of mean normal activity. Five patients were on ERT at the start of the study and 4 were ERT-naïve or pseudo-naïve. Four patients withdrew as of the cutoff date and the last patient has withdrawn since.

Isaralgagene civaparvovec has continued to be well-tolerated in all patients across cohorts. Save 1 instance of grade 2 pyrexia, all treatment-related adverse events (AEs) were grade 1. There have been no proactive or reactive steroid treatments.

Two patients with the most significant elevations in plasma globotriaosylsphingosine (lyso-Gb3) had 40% and 55% reductions from baseline after treatment. Several other patients experienced some increases in plasmalyso-Gb3 after withdrawing from ERT, but no patients have resumed ERT, and α-Gal A has remained elevated.

The open-label, multicenter, dose-ranging, STAAR study is enrolling patients with Fabry disease who are ERT-naïve, pseudo-naïve, or on ERT to evaluate the safety and tolerability of isaralgagene civaparvovec. The nine patients enrolled so far range in age from 22 to 51 years. The therapy has received orphan drug designation from the FDA and orphan medicinal product designation from the EMA.

“We continue to be excited by the promising data coming from our wholly owned Fabry program. The sustained levels of α-Gal A activity after ERT withdrawal suggest that ST-920 has the potential to provide an alternative to the current standard of care,” Nathalie Dubois-Stringfellow, PhD, senior vice president and chief development officer, Sangamo, added to the statement. “As we prepare for a potential Phase 3 trial, we look forward to sharing additional data from the nine dose escalation patients as well as our newly initiated expansion phase.”

Since the cutoff date, the STAAR study has transitioned into the expansion phase and has dosed the first 4 patients in this phase including the first female patient. Sangamo is planning for a potential phase 3 clinical trial.

Sangamo Therapeutics announces updated preliminary phase 1/2 data in Fabry disease showing continued tolerability and sustained elevated α-Gal Aenzyme activity in nine patients. News release. Sangamo Therapeutics. October 12, 2022.
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