Abeona Therapeutics announces new phase 1/2 safety and biopotency data of investigational gene therapy for Sanfilippo syndrome.
Abeona Therapeutics Inc., a clinical-stage biopharmaceutical company focused on developing novel cell and gene therapies for life-threatening rare genetic diseases, reported preliminary 30-day safety and biopotency signals from the first patient dosed in the company’s ongoing Phase 1/2 trial for ABO-101, a gene therapy treatment for patients with MPS IIIB (Sanfilippo syndrome Type B), enrolling at Nationwide Children’s Hospital in Columbus, Ohio.
The ABO-101 therapy involves a single intravenous injection of AAV gene therapy for subjects with MPS IIIB, a rare autosomal recessive disease causing neurocognitive decline, speech and mobility loss, and premature death. Abeona plans to enroll a total of three patients in Cohort 1 (2E13 vg/kg) before dose-escalating to the Cohort 2 dose (5E13 vg/kg).
“MPS IIIB is a devastating and progressive lysosomal storage disease with no approved treatment options,” Kevin M. Flanigan, M.D., principal investigator and director of the Center for Gene Therapy at Nationwide Children’s Hospital, said. “The first patient treated with ABO-101 has demonstrated that the systemic AAV gene transfer is well-tolerated, and the preliminary evidence of biopotency in the CNS and periphery is very encouraging.
“We are especially pleased to see reductions in several key biopotency markers, including the reductions in cerebral spinal fluid, urine and plasma heparan sulfate and normalization of plasma NAGLU enzyme activity at days seven, 14, and 30 post-transfer,” added Flanigan, who also serves as professor of pediatrics and neurology at The Ohio State University College of Medicine.
The Phase 1/2 study is designed to evaluate safety and preliminary indications of efficacy of ABO-101 in subjects suffering from MPS IIIB. In the first patient treated in Cohort 1:
• ABO-101, at a systemic dose of 2E13 vg/kg, is well-tolerated, with no treatment related adverse events or serious adverse events (SAEs) through 30 days of follow up.
• Early biopotency signals include significant heparan sulfate (HS) reductions observed in cerebral spinal fluid (50 percent), urine (69 percent), plasma (60 percent) and urinary total glycosaminoglycan (GAG) (67 percent).
- 50 percent decline in CSF heparan sulfate from baseline supports previous AAV9 clinical observations that ABO-101 crossed the blood brain barrier after intravenous administration.
• Normalized NAGLU enzyme activity observed represented by a greater than 300-fold increase over baseline at 30 days post administration.
“The reduction of heparan sulfate, the key biomarker of disease pathology in MPS IIIB, at 30 days post gene transfer indicates early and robust systemic delivery of ABO-101, and further supports our planned approach using intravenous delivery of ABO-101 in the treatment of Sanfilippo syndromes,” Timothy J. Miller, Ph.D., president and CEO of Abeona Therapeutics, said. “Consistent with our ongoing ABO-102 clinical trial in MPS IIIA, these findings support our plans to continue enrollment in this trial pending review by the DSMB.”
Subjects in the Phase 1/2 trial receive a single, intravenous injection of ABO-101, which uses an AAV vector to introduce a corrective copy of the NAGLU gene associated with MPS IIIB disease.
Subjects will be evaluated at multiple time points over the initial 30 days post-injection for safety assessments and initial signals of biopotency. Results in the first patient dosed with ABO-101 suggest strong CNS and broader systemic distribution, with the potential to reduce levels of glycosaminoglycans (GAGs) that represent the lysosomal storage pathology central to MPS IIIB disease progression.
ABO-101 has been granted Rare Pediatric Disease Designation in the U.S., and Orphan Product Designation in both the U.S. and the European Union.
(Source: Abeona Therapeutics Inc.)
Filed Under: Drug Discovery