RARE Daily

FDA Grants Fast Track Designation to Sio Gene Therapies’ Treatment for GM1 Gangliosidosis

October 26, 2021

The U.S. Food and Drug Administration granted Fast Track designation to Sio Gene Therapies’ AXO-AAV-GM1, its AAV9-based gene therapy candidate for the treatment of type I, early infantile onset, and type II, late infantile-onset and juvenile-onset, GM1 gangliosidosis.

Photo: Pavan Cheruvu, CEO of Sio Gene Therapies

The Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

“Receiving Fast Track designation is a critical step in our mission to develop the first potential treatment for all pediatric forms of this rare, terminal disease. This designation joins both the Orphan Drug designation and Rare Pediatric Disease designation assigned to AXO-AAV-GM1 by the FDA, which we believe further demonstrates the potential impact of this work on the patient community,” said Pavan Cheruvu, CEO of Sio Gene Therapies. “Building on the recently presented data at ESGCT demonstrating normalization of key disease biomarkers in the high-dose cohort with no serious adverse events attributed to AXO-AAV-GM1, this designation will help us accelerate clinical development of this promising investigational therapy for children and families.”

GM1 gangliosidosis (GM1) is a lysosomal storage disorder 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. GM1 manifests as a continuum of disease and is most severe in the Type I infantile form, which is characterized by onset in the first six months of life by reduced muscle tone, progressive central nervous system dysfunction, and rapid developmental regression. Currently, there are no FDA-approved treatment options for GM1 gangliosidosis.

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.

The current phase 1/2 study is designed to evaluate the safety, tolerability, and potential efficacy of AXO-AAV-GM1 gene therapy delivered intravenously in children with early infantile, or Type I, and late infantile and juvenile, or Type II, GM1 gangliosidosis. Stage 1 of the study is a dose-escalation study in which the low-dose cohort is evaluating 1.5×1013 vg/kg and the high-dose cohort is evaluating a dose of 4.5×1013 vg/kg. Stage 2 of the trial will then evaluate the efficacy and safety of the optimal dose identified in Stage 1.

In 2018, Sio licensed exclusive worldwide rights from UMass Chan Medical School for the development and commercialization of gene therapy programs for GM1 gangliosidosis and GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases.

Author: Rare Daily Staff

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