Axovant Presents First Evidence of Clinical Stabilization in Tay-Sachs Disease at the European Society of Gene and Cell Therapy 27th Annual Congress
- Initial data with AXO-AAV-GM2 suggests stabilization of disease course, attainment of normal developmental milestones, and improvement in myelination on brain MRI
- AXO-AAV-GM2 generally safe and well-tolerated to date
- Additional data to be presented by Dr.
Terence Flotteat 5:30 PM CETtoday during ESGCT
“Today’s exciting clinical results from the AXO-AAV-GM2 program are the first reported evidence for potential disease modification in Tay-Sachs disease, and suggest an opportunity for gene replacement therapy to improve outcomes for children with this devastating condition,” said Dr.
Key findings from this first-in-human study in patients treated with AXO-AAV-GM2, an investigational gene therapy designed to restore β-Hexosaminidase A enzyme activity in the central nervous system, include:
- AXO-AAV-GM2 was successfully administered in both patients and has been generally well-tolerated to date, with no serious adverse events or clinically-relevant laboratory abnormalities related to therapy.
- First child with advanced infantile TSD, dosed in
November 2018, is clinically stable at 41 months of age (11 months after dosing). Patient had severe, advanced disease at time of dosing.
- Route of administration included cisterna magna (CM) and lumbar region delivery via intrathecal catheter. Intra-thalamic dosing was not possible due to the patient’s advanced disease.
- Observed maintenance of motor skills, as measured by the
Children's Hospitalof Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND*), with baseline total score of 14 increased to a total score of 18 at month 6 following gene transfer and ranged between 14-18 from week 1 to month 6 (latest data point collected).
- Hex A enzyme activity in cerebrospinal fluid (CSF) increased by approximately 3-fold at month 3 and month 6 relative to baseline.
- Second child with infantile-onset TSD, dosed in
June 2019, is clinically stable at 11 months of age (4 months after dosing). Patient was dosed with gene therapy prior to onset of severe symptoms.
- The route of administration was bilateral intraparenchymal thalamic and intracisternal/intrathecal.
- Clinical disease stabilization was observed in the treated child, with attainment of normal developmental milestones and a normal neurologic exam at 10 months of age.
- No seizure activity and no exaggerated startle responses were observed.
- By contrast, the patient’s untreated, two older siblings with TSD exhibited rapid disease progression, clinical regression and seizure onset at 10-12 months of age.
- Brain MRI taken at 10 months of age demonstrated normal brain anatomy and increased myelination, consistent with normal brain development at this age.
- By contrast, commonly reported MRI findings in infantile TSD at this age include demyelination and cerebral and cerebellar atrophy.
- CHOP INTEND total score was 58 at baseline, increased to a total score of 60 at month 3 following gene transfer and ranged between 58-61 from week 2 to month 3.
- Hex A enzyme activity in CSF increased to 1.8% of normal enzyme activity between baseline and 3 months (a sustained level ≥ 0.5% of normal enzyme activity is expected to correlate with a clinically meaningful effect).
*CHOP INTEND is a 16-item scale of motor function that has been validated in infants with neuromuscular disorders. Items of motor function are graded from 0 to 4 for each item, where zero equals no response, and 4 equals a complete response. Change from baseline in total score of ≥ 4 points or a total score sustained > 40 points has been associated with a clinically meaningful benefit.
Dr. Flotte will present this data on AXO-AAV-GM2 in the First-in-Human gene therapy session on
AXO-AAV-GM2 is an investigational gene therapy for Tay-Sachs and Sandhoff disease, which rare and fatal pediatric neurodegenerative genetic disorders within the GM2 gangliosidosis family, caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the β-hexosaminidase A (HexA) enzyme. Both forms of GM2 gangliosidosis are caused by overwhelming storage of GM2 ganglioside within neurons throughout the central nervous system), which is normally degraded in the lysosome by the isozyme HexA. These genetic defects lead to progressive neurodegeneration and shortened life expectancy. AXO-AAV-GM2 aims to restore HexA levels by introducing a functional copy of the HEXA and HEXB genes via delivery of two co-administered AAVrh8 vectors.
In 2018, Axovant licensed exclusive worldwide rights from the
Axovant is focused on accelerating product candidates into and through clinical trials with a team of experts in gene therapy development and through external partnerships with leading gene therapy organizations. For more information, visit www.axovant.com.
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Research into potential therapies for lysosomal storage diseases such as Tay-Sachs, Sandhoff disease and GM1 gangliosidosis at
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