Abstract Details

Title Updated results of Transpher A, a multicenter, single-dose, Phase 1/2 clinical trial of ABO-102 investigational gene therapy for Sanfilippo syndrome type A (mucopolysaccharidosis IIIA)

Topic Child Neurology and Developmental Neurology

Presentation(s) S39 - Child Neurology and Developmental Neurology (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Objective Transpher A (NCT02716246) is a Phase 1/2 clinical trial assessing the safety and efficacy of investigational gene therapy ABO-102, an scAAV9-based vector encoding hSGSH. After 24 months of active posttreatment monitoring, patients are transferred to a long-term follow-up study for 3 years.

Background MPS IIIA is a fatal neurodegenerative lysosomal storage disorder that manifests early in childhood, with no clinically approved treatments.

Design/Methods Primary endpoints are safety and neurocognitive development (versus natural history). Secondary endpoints include cognitive and behavior evaluations, biomarkers, and brain and liver volume. Twenty-one patients have been enrolled across three dose cohorts: Cohort 1, 5×10¹² vg/kg, n=3; Cohort 2, 1×10¹³ vg/kg, n=3; Cohort 3, 3×10¹³ vg/kg, n=15. ABO-102 was well tolerated, with no serious drug-related adverse events (follow-up: Cohort 1, 56.5-59.7 months; Cohort 2, 48.5-51.1 months; Cohort 3, 0.5-45 months).

Results

Cohort 3 was associated with rapid, dose-dependent, sustained, and statistically significant reductions in cerebrospinal fluid heparan sulfate and statistically significant reductions in systemic biomarkers and liver volumes for the duration of follow-up. Younger patients (≤30 months, DQ>60) showed preservation of neurocognitive development within normal range of an unafflicted child 30-36 months post administration. Preliminary MRI findings from the three patients in Cohort 3 who have reached 24 months posttreatment (when MRI data are analyzed) showed an increase in cortical gray matter, corpus callosum, and amygdala volumes with ABO-102 treatment compared with natural history data.

Conclusions

Investigational ABO-102 in patients with MPS IIIA showed a favorable long-term safety profile and led to significant reductions in central nervous system and systemic biomarkers (Cohort 3), with clear indications of meaningful neurocognitive benefit in the youngest patients treated before advanced neurodegeneration.

Authors/Disclosures
Kevin M. Flanigan, MD, FAAN (Nationwide CHildrens Hospital) PRESENTER	Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Solid. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Armatus. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Flanigan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne. The institution of Dr. Flanigan has received research support from Ultragenyx . The institution of Dr. Flanigan has received research support from Solid Biosciences. The institution of Dr. Flanigan has received research support from Dyne Therapeutics. The institution of Dr. Flanigan has received research support from Avidity.
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J Ruiz	J Ruiz has received personal compensation for serving as an employee of Abeona Therapeutics. J Ruiz has received stock or an ownership interest from Abeona Therapeutics.
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Igor Grachev	No disclosure on file

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