Abstract Details

MPS-IIIA is a lysosomal storage disorder manifesting early in childhood with severe neurodegeneration.

To assess the efficacy and safety of ABO-102 in children with Mucopolysaccharidosis IIIA (MPS-IIIA).

Transpher A is a Phase 1/2 clinical trial assessing the safety and efficacy of a single intravenous administration of ABO-102, a self-complementary AAV9-based vector encoding human SGSH, for treating MPS-IIIA. After 24 months, patients are transferred to a Long-Term Follow-Up study where they are monitored for 3 subsequent years. Primary endpoints are safety and neurocognitive development (compared to natural history studies), and secondary endpoints include additional cognitive and behavior evaluations as well as biomarker determination of brain and liver volume.

Nineteen patients have been enrolled across three dose cohorts: Cohort 1, 5x10¹² vg/kg, n=3; Cohort 2, 1x10¹³ vg/kg, n=3; Cohort 3, 3x10¹³ vg/kg, n=13. Cohorts 1 and 2, and 8 of 13 patients in Cohort 3 have completed 24-month follow-up. ABO-102 was well tolerated, with no serious drug-related adverse events (Follow-up Cohort 1: 53.5-56.7 months: Cohort 2: 45.5-48.1 months; Cohort 3: 1-42 months). Cohort 3 (the highest dose) was associated with rapid, dose-dependent, and statistically significant reductions of CSF heparan sulfate (HS) at all time points (including Month 24), as well as statistically significant reductions for systemic biomarkers (plasma and urine HS and total urine glycosaminoglycans) and liver volumes for the duration of follow-up. Neurocognitive evaluation showed continuous developmental progress 30-36 months post-administration (43, 48 and 64 months of chronological age), a time at which they should be experiencing cognitive decline.

ABO-102 in MPS-IIIA patients showed a favorable long-term safety profile and led to statistically significant reductions in CNS and systemic biomarkers, with clear indications of meaningful neurocognitive benefit in the youngest patients treated with 3x10¹³ vg/kg, before advanced neurodegeneration.