RARE Daily

Sio Gene Therapies Reports Positive Early Data from Gene Therapy for GM1 Gangliosidosis

December 16, 2020

Rare Daily Staff

Sio Gene Therapies (formerly Axovant) reported six-month follow-up data from a study of its gene therapy AXO-AAV-GM1 for the rare and fatal pediatric disorder GM1 gangliosidosis that showed it was able to stabilize disease progression and in some cases improve the condition.

The data from the ongoing phase 1/2 study involved five patients in the low-dose cohort.

GM1 gangliosidosis (GM1) is a progressive and often life-threatening monogenic recessive disease caused by mutations in the GLB1 gene, which encodes lysosomal acid beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of toxic levels of GM1 ganglioside in neurons throughout the brain, causing rapidly progressing neurodegeneration.

AXO-AAV-GM1 delivers a functional copy of the GLB1 gene via an adeno-associated viral (AAV) vector, with the goal of restoring β-galactosidase enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is delivered intravenously, which has the potential to broadly transduce the central nervous system and treat peripheral manifestations of the disease as well. AXO-AAV-GM1 has received both Orphan Drug designation and Rare Pediatric Disease designation from the U.S. Food and Drug Administration and is the only gene therapy in clinical development for both type I and type II GM1 gangliosidosis.

The company said it saw encouraging safety, tolerability, biomarker, and preliminary efficacy data for AXO-AAV-GM1. It said it saw an increase in beta-galactosidase enzymatic activity, reaching on average 38 percent of normal reference levels. Medical literature suggests that for lysosomal storage diseases, increases in enzyme activity of between 10 to 20 percent of normal levels can lead to clearance of stored lysosomal substrates and may be associated with slower disease progression.

“We are also encouraged by consistent signs of disease stabilization across multiple measures of neurodevelopment in all five children at six months as compared to the predictable decline observed in natural history studies,” said Gavin Corcoran, chief R&D officer of Sio Gene Therapies. “These data highlight the potential for the investigational gene therapy to treat the underlying genetic cause of this disease, preserve functional outcomes, and reduce disease burden for patients and their families.”

Sio said the safety profile observed in the low-dose cohort supports moving forward with the high-dose cohort in the ongoing phase 1/2 study, which is designed to evaluate the safety, tolerability, and potential efficacy of AXO-AAV-GM1 delivered intravenously in children with type I and type II GM1 gangliosidosis.

Photo: Gavin Corcoran, chief R&D officer of Sio Gene Therapies

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