MRI Data Supports Gene Therapy for Sanfilippo Syndrome Type A


Abeona Therapeutics is seeking a path towards BLA filing based on the promising clinical data.

New magnetic resonance imaging (MRI) data of ABO-102 (Abeona Therapeutics) for the treatment of mucopolysaccharidosis Type 3 A (Sanfilippo Syndrome Type A) showed that the gene therapy increased grey matter, corpus callosum, and amygdala volumes in the brain in 3 patients at 24 months compared with placebo.1

The data are from the phase 1/2 Transpher A clinical study (ABT-001; NCT02716246) and was presented during an oral presentation at the 16th International Symposium on MPS and Related Diseases. The study is evaluating neurodevelopment and safety primary end points and efficacy secondary end points such as brain volume, behavior evaluations, quality of life, enzyme activity in cerebrospinal fluid (CSF) and plasma, heparan sulfate levels in CSF, plasma and urine, and liver volume.

“Brain volume loss is characteristic in children with MPS IIIA and is associated with long-term cognitive and physical disability. Specifically, grey matter is important for cognitive development, corpus callosum for motor function, and amygdala for fear learning as well as social/emotional development,” said Vishwas Seshadri, PhD, MBA, head of research and clinical development, Abeona, in a statement.

ABO-102 is a one-time gene therapy administered via intravenous infusion. It uses a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to central nervous system cells and peripheral organs. The therapy is designed to correct the underlying SGSH enzyme deficiency that causes abnormal accumulation of glycosaminoglycans in the brain and throughout the body, hopefully halting the progressive cell damage and neurodevelopmental and physical decline seen in the disease’s natural history.

READ MORE: RGX-121 Advances to Final Cohort in Phase 1/2 MPS-II Study

The Transpher A study, also known as ABT-001, is an ongoing, 2-year, open-label, dose-escalation, Phase 1/2 global clinical trial. The study is currently recruiting patients from birth to age 2, or patients older than 2 years with a cognitive developmental quotient of 60% or above.

“The new MRI data shows the potential of ABO-102 to increase brain grey matter, corpus callosum and amygdala volumes and is consistent with previously reported results of preservation of neurocognitive development in these three young patients in the Transpher A study,” Seshari added.

The FDA has previously granted regenerative medicine advanced therapy, fast track, rare pediatric disease, and orphan drug designations to ABO-102. The FDA accepted Abeona’s request to meet for a potential path toward a biologics license application based on clinical findings presented on ABO-102 at WORLDSymposium in February 2021.2

Abeona presented data from 18 patients across 3 cohorts treated with ABO-102: cohort 1 (ABO-102 at 5x1012 vg/kg [n = 3]), cohort 2 (1x1013 vg/kg [n = 3]), and a high-dose cohort 3 (3x1013 vg/kg [n = 12]). At the time of data presentation, all patients from cohorts 1 and 2, and 8 patients from cohort 3 had completed the 24-month follow-up period.

Investigators found that neurocognitive development was preserved within normal range of a non-afflicted child for 2.5 years to 3 years after treatment with ABO-102 (3x1013 vg/kg) in 3 patients. The participants were 27 months, 19 months, and 12 months at the time of treatment and are now 3, 5, and over 5 years of age, ages at which natural history of MPS type 3 A would dictate neurocognitive decline. 

Dose-dependent and statistically significant reductions in cerebrospinal fluid heparan sulfate and liver volume were sustained for 2 years after treatment. ABO-102 remains well-tolerated with favorable long-term safety observed 24-55 months following treatment. No treatment-related severe adverse events (AEs) or clinically significant AEs have been reported.

“We are excited to share updated positive efficacy and safety results that continue to suggest ABO-102 has the potential to be a life-altering treatment option for children with MPS IIIA, a rare, debilitating condition with no approved treatment that leads to progressive neurodevelopmental and physical decline, and often results in death early in life. We have requested a meeting with the FDA later this quarter to discuss the ABO-102 data and the potential path towards a Biologics License Application filing for ABO-102. In addition, the new results from the Transpher B study continue to support ABO-101’s biologic activity in patients with MPS IIIB,” Michael Amoroso, principal executive and chief operating officer, Abeona, said in a previous statement.2

1. Abeona Therapeutics announces new MRI data showing increased brain volume in young patients with Sanfilippo Syndrome Type A (MPS IIIA) after treatment with ABO-102 gene therapy. News release. Abeona Therapeutics. July 26, 2021.
2. Data presented at WORLDSymposium™ shows neurocognitive development of young MPS IIIA patients preserved up to three years following treatment with Abeona’s ABO-102 gene therapy. News release. Abeona Therapeutics. February 12, 2021.
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