Rare Disease Report

MPS IIIA Gene Therapy, ABO-102, Shows Efficacy in Trial Update

MAY 18, 2018
Krista Rossi
This morning, Abeona Therapeutics Inc. released positive data from its phase 1/2 trial for ABO-102 (AAV-SGSH), a clinical gene therapy for the treatment of Sanfilippo syndrome type A (MPS III A). The data were presented at the 21st Annual Meeting of the ASGCT (American Society for Gene and Cell Therapy) in Chicago, Illinois.

“Children with MPS IIIA experience devastating quality of life consequences including neurocognitive decline, speech and mobility loss, and premature death,” commented Carsten Thiel, PhD, CEO of Abeona in a recent statement. “As a leader in gene therapy for MPS IIIA patients, we feel encouraged by the strong data demonstrated thus far in this trial, showing significant dose- and time-dependent improvement of the underlying disease pathology. With the recently granted RMAT designation, we look forward to continuing our regulatory discussions to advance this promising therapy for patients.”

Throughout various time points post-administration, the ongoing trial results from ABO-102 (AAV-SGSH) show effective, strong, and achievable clinical results. As of the present, 11 patients have been administered a single intravenous injection of ABO-102.

ABO-102 is an adeno-associated viral (AAV)-based gene therapy. It is a one-time treatment that delivers a normal copy of the defective gene to cells of the central nervous system. Reversing the effects of the genetic errors that cause the disease is its primary aim.

MPS IIIA is a rare, autosomal-recessive, lysosomal storage disease that is characterized by the accumulation of the heparan sulfate.

Each participant was administered a single intravenous injection of ABO-102 for a systemic delivery of a functional copy of the missing SGSH gene associated with disease onset and progression.  

Selected data included significant demonstrations of dose-dependent and time-dependent responses in key biomarkers through 18-months post-injection, including sustained reductions of heparan sulfate, which is the sugar molecule that is the hallmark of MPS IIIA, in the cerebral spinal fluid (CSF) and urine.

CSF heparan sulfate and urine heparan sulfate assessments were primary measures in the trial. Each metric was measured in 3 cohorts; however, later measures did dwindle to include only 1 or two cohorts in some cases.

At the day 30 assessment, CSF heparan sulfate demonstrated a 25.8% reduction in cohort 1 (n=3), a 52.1% reduction in cohort 2 (n=3), and a 67.1% reduction in cohort 3 (n=4). At the day 180 assessment,it demonstrated a 58.7% reduction in cohort 1 (n=3), a  60.5% reduction in cohort 2 (n=3), and an 83.3% reduction in cohort 3 (n=1). At the day 360 assessment, it demonstrated a 69.3% reduction in cohort 1 (n=2) and a 65.7% reduction in cohort 2 (n=2).

At the day 30 assessment, urine heparan sulfate demonstrated 64.2% reduction in cohort 1 (n=3), a 54% reduction in cohort 2 (n=3), and a 90.3% reduction in cohort 3 (n=3). At the day 90 assessment, it demonstrated a 54.2% reduction in cohort 1 (n=3), a  63.1% reduction in cohort 2 (n=3), and 77.1% reduction in chort 3 (n=4). At the day 180 assessment, it demonstrated a 29.2% reduction in cohort 1 (n=3), a 57.6% reduction in cohort 2 (n=2), and a 75% reduction in cohort 3 (n=1). At the day 360 assessment, it demonstrated 29.2% reduction in cohort 1 (n=3) and a 45.1% reduction in cohort 2 (n=2). At the day 540 assessment, it demonstrated a 30% reduction in cohort 1 (n=3).

To date, ABO-102 has been well-tolerated in all subjects, with no drug-related serious adverse events (SAE) reported through over 4,200 cumulative days post-injection. It has also been granted Regenerative Medicine Advanced Therapy, Rare Pediatric Disease, and Fast Track designations in the United States and Orphan Product Designation in both the United States and the European Union.

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