Abeona Therapeutics Inc., a leading clinical-stage biopharmaceutical company focused on developing novel cell and gene therapies for life-threatening rare genetic diseases, announced updated clinical data from the ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH), the company’s investigational gene therapy for the treatment of Sanfilippo syndrome Type A (MPS IIIA), a rare autosomal-recessive lysosomal storage disease. The results demonstrate robust and durable clinical effects achieved throughout various timepoints post-administration. To date, 10 patients have been dosed with a single intravenous injection of ABO-102. Results were reported today during the WORLDSymposium for Lysosomal Diseases being held this week in San Diego, CA.
“MPS IIIA is a profound and deadly lysosomal storage disease with no approved treatments available. The encouraging clinical data reported today provide strong additional support for a whole-body treatment approach involving intravenous delivery of an AAV to drive expression of the SGSH enzyme in all organs of the body, with an emphasis on expression in the central nervous system,” stated Kevin M. Flanigan, M.D., principal investigator of the trial, director of the Center for Gene Therapy at Nationwide Children’s Hospital and professor of pediatrics and neurology at The Ohio State University College of Medicine. “We are especially pleased to see sustained decreases in CSF heparan sulfate in all subjects post-injection, along with positive signals of neurocognitive activity in Cohorts 1 and 2.”
In the trial, subjects received a single intravenous injection of ABO-102 to facilitate systemic delivery of a corrective copy of the gene associated with onset and progression of MPS IIIA. Subjects were evaluated at multiple time points post-injection for safety assessments and signals of biopotency and clinical activity.
“Results thus far from the ongoing ABO-102 clinical trial support the tolerability of a systemically delivered AAV approach for the treatment of lysosomal storage diseases,” stated Timothy J. Miller, Ph.D., president and CEO of Abeona Therapeutics. “The large reductions in heparan sulfate in both CSF and urine, significant organ changes and demonstration of neurocognitive benefits represent important findings that support our path to regulatory guidance later this year. Importantly, the FDA recently allowed the lowering of the enrollment age to include subjects as young as 6 months, supporting the clinical paradigm of treating subjects earlier in their disease manifestation.”
Select updated data from the presentation are highlighted below, and the full presentation is available here: https://
Biopotency Assessments: ABO-102 continues to demonstrate significant dose-dependent and time-dependent responses in measured biomarkers, including rapid and sustained reductions of heparan sulfate (HS), the sugar molecule that is the hallmark of MPS IIIA, in the cerebral spinal fluid (CSF) and urine.
CSF heparan sulfate:
- Day 180 assessment
- Cohort 2 (n=3) demonstrated a reduction of 57.1% +/- 7.14%
- Day 30 assessment
- Cohort 3 (n=3) demonstrated a reduction of 64.4% +/- 2.2%
Urine heparan sulfate (HS):
- Day 30 assessment
- Cohort 3 (n=3) demonstrated a reduction of 91.9% +/-1.5%
- Cohort 2 (n=3) demonstrated a reduction of 54.0% +/- 18.0%
- Day 60 assessment
- Cohort 3 (n=4) demonstrated a reduction of 73.4% +/- 13.5%
- Cohort 2 (n=3) demonstrated a reduction of 65.2% +/- 5.5%
- Day 90 assessment
- Cohort 3 (n=1) demonstrated a reduction of 94.9 %
- Cohort 2 (n=3) demonstrated a reduction of 63.1%+/- 8.2%
- Day 180 assessment
- Cohort 2 (n=2) demonstrated a reduction of 55.0% +/- 5.0%
- Cohort 1 (n=2) demonstrated a reduction of 29.2% +/- 35.6%
Biophysical Assessments: A separate natural history study (Truxal et. al., 2016, Mol. Genet. Metab.) of MPS IIIA demonstrated that subjects showed an average 220% increase in liver volume at baseline. Result from the Phase 1/2 clinical trial for ABO-102 demonstrate durable biophysical reductions of disease burden including reductions in liver volume.
Cognitive Assessments: ABO-102 continues to show evidence of stabilization or improvement in cognitive function at six months in Cohort 2 and one year in Cohort 1.
- Two of the three treated patients from Cohort 2 showed evidence of improvement in the Leiter-R non-verbal IQ and stabilized Vineland (adaptive behavior) scales.
Safety Assessments: ABO-102 is well-tolerated in all subjects to date, with no drug-related serious adverse events (SAE) reported through over 3,100 cumulative days post-injection.
ABO-102 has been granted Rare Pediatric Disease Designation and Fast Track Designation in the U.S. and Orphan Product Designation in both the USA and the European Union.