Axovant Licenses Investigational Gene Therapies for GM1 Gangliosidosis, Tay-Sachs and Sandhoff Diseases from University of Massachusetts Medical School
- Two novel programs for fatal pediatric diseases deepen Axovant’s neurological gene therapy pipeline
- AXO-AAV-GM1 expected to enter the clinic in first half 2019, with initial data expected in second half 2019
- First patient has been dosed with AXO-AAV-GM2, with initial data expected in first quarter 2019
GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases are rapidly progressive and fatal pediatric lysosomal storage disorders that reduce life expectancy to less than two to four years of age in the severe forms of the diseases. GM1 gangliosidosis has an incidence of approximately one out of 100,000 live births worldwide, and Tay-Sachs and Sandhoff diseases have an incidence of approximately one out of 180,000 live births worldwide. GM1 gangliosidosis is caused by defects in the GLB1 gene and GM2 gangliosidosis is caused by defects in the HEXA (leading to Tay-Sachs disease) and HEXB (leading to Sandhoff disease) genes, resulting in impaired enzyme function and the accumulation of toxic gangliosides primarily in the central nervous system.
AXO-AAV-GM1 and AXO-AAV-GM2 are each designed to introduce functional copies of the respective genes encoding the critical enzymes impacted in these diseases, with an aim to improve survival and enable children to reach key developmental milestones. In prior animal studies conducted with these gene therapies, dose-dependent increases in enzyme activity, reductions in accumulated gangliosides and prolonged survival have been observed.
AXO-AAV-GM1 will be evaluated in an investigator-initiated clinical program conducted at the
The AXO-AAV-GM2 clinical program is ongoing with the first subject having been dosed with the therapy. Initial data from this program are expected in first quarter 2019 and we expect patients to be enrolled in a multi-subject clinical trial in 2019.
“Diseases like Tay-Sachs are attractive targets for the transformative possibilities of gene therapy because we have been able to identify the underlying genetic cause of the disease and now have well-understood methods of delivering the corrective genes,” said
“We are excited to add these potentially life-saving gene therapy programs for GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases to our growing pipeline of innovative gene therapy product candidates. The devastating nature of these disorders creates an urgent need to pursue opportunities that may offer hope to these children and their families,” said Pavan Cheruvu, M.D., chief executive officer of Axovant. “We look forward to working with world-recognized pioneers in gene therapies at the
“We have lost too many children to these devastating diseases. Patients and their families deserve the hope that these potentially life-saving gene therapies could provide,” said
In exchange for these exclusive worldwide licenses for the gene therapy programs for GM1 and GM2 gangliosidoses, Axovant will be making payments to
About the Collaboration with
Research into the causes and potential therapies for lysosomal storage diseases such as Tay-Sachs, Sandhoff diseases and GM1 gangliosidosis at
“We are enthusiastic to partner with Axovant and its experienced team in the treatment of GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases,” said
About GM1 Gangliosidosis, Tay-Sachs and Sandhoff Diseases
GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases are a set of rare and fatal neurodegenerative genetic disorders caused by impaired β-galactosidase (β-gal) and β-hexosaminidase A (Hex A) enzyme activity, respectively. GM1 gangliosidosis is caused by defects in the GLB1 gene, which encodes the β-gal enzyme. GM2 gangliosidosis, including Tay-Sachs and Sandhoff diseases, is caused by defects in the HEXA (leading to Tay-Sachs disease) and HEXB (leading to Sandhoff disease) genes that encode the two subunits of the Hex A enzyme. Defects in these genes cause impaired enzyme activity leading to the toxic accumulation of gangliosides, resulting in neurodegeneration that presents as cognitive impairment, paralysis and early death. There are currently no disease-modifying treatments for these diseases and children born with these disorders mostly have a life expectancy shortened to two to four years of age.
About the AXO-AAV-GM1 Program
AXO-AAV-GM1 delivers a functional copy of the GLB1 gene via an adeno-associated viral (AAV) vector, AAV9, which is effective in crossing the blood-brain barrier and transducing neurons, with the goal of restoring β-gal 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. In preclinical studies, AXO-AAV-GM1 was shown to improve β-gal enzyme activity, reduce GM1 ganglioside accumulation, improve neuromuscular function, and extend survival. Magnetic resonance imaging (MRI) of felines with GM1 gangliosidosis treated with GM1 gene therapy showed normal brain architecture through at least two years of age.
About the AXO-AAV-GM2 Program
AXO-AAV-GM2 delivers functional copies of the HEXA and HEXB genes via two, co-administered AAVrh8 vectors delivered directly to the central nervous system with the goal of restoring Hex A enzyme activity to address both Tay-Sachs and Sandhoff diseases. The preclinical data for AXO-AAV-GM2 in murine models showed dose-dependent increases in Hex A enzyme activity, reductions of GM2 gangliosides in the brain and prolonged survival rates. A next-generation gene therapy for Tay-Sachs and Sandhoff diseases aimed at enabling systemic intravenous administration is in earlier-stage development.
Axovant is a clinical-stage gene therapy company focused on developing a pipeline of innovative product candidates for debilitating neurological diseases such as Parkinson's disease, GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases, oculopharyngeal muscular dystrophy (OPMD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and other indications. For more information, visit www.axovant.com
Forward-Looking Statements and Information
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Source: Axovant Sciences Ltd.