dm+d

Unassigned

New Medicines

Fabry's disease

Information

New molecular entity
Sangamo
Sangamo

Development and Regulatory status

Phase II Clinical Trials
None
Phase II Clinical Trials
Yes
Yes
May 22Has orphan drug status in the EU and US [3].

Category

An in vivo recombinant adeno-associated virus2/6 (AAV) human alpha galactosidase A (GLA) gene therapy. Deficiency of the enzyme α-galactosidase A (α-Gal A) causes Fabrys disease as it results in the toxic buildup of the fatty substance ganglioside globotriaosylceramide (Gb3) and lyso-Gb3. The candidate utilises AAV to deliver the cDNA for α-Gal A toliver cells that enables the liver to produce and secrete active α-Gal A enzyme into the bloodstream to be taken up by other tissues.
It is estimated to occur in 1 in 55,000 males in the classical form but the atypical variant may be more common. It has been described in many racial groups. As an X-linked recessively inherited condition, female carriers exist and can exhibit mild-to-moderate symptoms (variable expression according to random X inactivation of the affected gene in embryogenesis) [1].
Fabry's disease
Intravenous infusion

Trial or other data

Apr 22PI/II trial is recruiting [2].
Feb 22Results from the PI/II STAAR trial from four patients treated in first two cohorts for isaralgagene civaparvovec (0.5e13 vg/kg and 1e13 vg/kg) showed that all four patients exhibited above normal alpha-galactosidase A (a-Gal A) activity, ranging from 2-fold to 15-fold above mean normal at last measurement as of 09 November 2021 cutoff date. In a patients in cohort 1, a-Gal A activity measured at ERT trough was 15-fold above mean normal at week 52 and in another patients from cohort 2, the enzyme activity was 10-fold above mean normal at week 25. For the two ERT pseudo-naïve patients, a-Gal A activity was 3-fold above mean normal at week 52 in Cohort 1 and 4-fold above mean normal at week 40 in Cohort 2. Early data available from a patients dosed at 3e13 vg/kg in third cohort showed that the a-Gal A activity has increased into mean normal range at week 2. Withdrawal from enzyme replacement therapy (ERT) has taken place for one patient and is planned for the other patient on ERT, based on the stability of their a-Gal A activity following treatment. The one patient with a significant elevation in plasma lyso-Gb3 pre-treatment showed significant reductions of approximately 40% (from baseline within 10 weeks after dosing, maintained through Week 32) in this biomarker after treatment with isaralgagene civaparvovec. Patients with low baseline levels of lyso-Gb3 maintained steady levels through the cutoff date. Isaralgagene civaparvovec treatment resulted in improvements in ability to sweat in the first three treated patients. there was no progression of Fabry cardiomyopathy in the two patients experiencing cardiomyopathy prior to treatment [3].
Jul 19PI/II STAAR trial to evaluate the safety and tolerability of ascending doses of isaralgagene civaparvovec in patients with Fabrys disease starts (NCT04046224; ST-920-201). The open-label, dose ranging study intends to enrol 18 adults in the US and UK (at Queen Elizabeth Hospital in Birmingham, Addenbrookes Hospital and the Royal Free Hospital). On Day 1, patients will be infused intravenously with a single dose of ST-920 and followed for a period of 52 weeks. Collection of primary outcome data (safety) is due to complete Dec 23 [2].