Fabry mice (GLA knockout) received a single dose of ssAAV8-FRE1-GLAco (FLT190 pseudotyped with AA8 capsid). The first assessment of GLA levels made at four weeks after dosing showed levels up to 1061-fold higher compared to wild-type mice. These GLA levels were maintained throughout the follow up period, up to 98 days after dosing. Importantly, this single administration led to significant and durable reductions in Gb3 storage levels in the heart and kidney, thus demonstrating reduction of this toxic metabolite in important organs frequently affected by Fabry Disease. No adverse clinical signs or toxicity associated with high expression of α-GLA in the liver or increased plasma exposure to GLA were observed in the study.
Freeline also presented the study design for MARVEL1, the Phase 1/2 clinical study of FLT190 in patients with Fabry Disease. This study investigates the safety of FLT190, a new gene therapy using the Freeline proprietary AAVS3 capsid. In addition, the study will investigate the potential of FLT190 in treating the signs and symptoms of Fabry Disease following a single administration, including e.g. αGLA activity levels, Gb3/Lyso-Gb3 clearance, changes in Gb3 in renal and skin biopsies, renal and cardiac function, GLA immune response, viral shedding and quality of life. The study is currently recruiting at two sites in Europe.
Anne Prener, Chief Executive Officer of Freeline said:
“Our preclinical data are very encouraging, demonstrating clear evidence of the therapeutic potential of FLT190 in treating Fabry Disease.”