information: Clinical trial authorisation
Announcement: clinical trial authorization
Company: Abeona Therapeutics (USA - NY)
Product: ABO-101 (AAV NAGLU)
- gene therapy. ABO-101 (AAV NAGLU) is a next generation adeno-associated viral (AAV)-based gene therapy for MPS IIIB. This gene therapy involves a one-time delivery of a genetically modified virus to deliver a normal copy of the defective gene to cells of the central nervous system and peripheral organs with the aim of reversing the effects of the genetic errors that cause the disease. After a single dose in preclinical animal models of Sanfilippo syndrome, ABO-101 induced cells in the CNS and peripheral organs to produce the missing enzymes and help repair damage caused to the cells. Preclinical in-vivo efficacy studies in animals with Sanfilippo syndrome have demonstrated functional benefits that remain for months after treatment. A single dose significantly restored normal cell and organ function, corrected cognitive defects that remained months after drug administration, increased neuromuscular control and increased the lifespan of animals with MPS III over 100% one year after treatment compared to untreated control animals.
- 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.
Disease: mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo syndrome Type B)
area: Rare diseases
Country: France, Germany, Spain, UK, USA
- Subjects in the Phase 1/2 trial receive a single, intravenous infusion of ABO-101, which uses an AAV vector to introduce the functional NAGLU gene to treat patients with MPS IIIB disease. Subjects will be evaluated at multiple time points post-injection for safety assessments and efficacy parameters. The clinical program is supported by a Natural History Study which included potential efficacy assessments consisting of neurocognitive evaluations, biochemical assays and MRI data generated over one year of follow-up assessments.
- • On September 12, 2018, Abeona Therapeutics announced authorization to move forward with a Phase 1/2 clinical trial in Spain for ABO-101 (AAV-NAGLU) for patients with MPS IIIB (Sanfilippo syndrome type B). The clinical study was approved by the Agencia Espanola de Medicamentos y Productos Sanitarios and is being conducted at Hospital Clinico Universitario of Santiago de Compostela, Spain. This will be the company’s second clinical trial conducted in Europe, alongside the ongoing Phase 1/2 clinical trial for patients with MPS IIIA (Sanfilippo syndrome type A). Abeona first initiated this trial in the United States. Abeona plans to add clinical sites for the trial in three European countries including France, Germany and the United Kingdom.
- • On February 7, 2018, Abeona Therapeutics 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). 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%), urine (69%), plasma (60%) and urinary total glycosaminoglycan (GAG) (67%).
- • 50% 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.
- 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.
- • On May 24, 2016, Abeona Therapeutics announced the FDA has allowed an Investigational New Drug (IND) Application for its phase 1/2 clinical study with gene therapy candidate ABO-101 (AAV-NAGLU) for patients with Sanfilippo syndrome type B (MPS IIIB) to be conducted at Nationwide Children's Hospital (Columbus, OH). This is the second FDA allowance for a gene therapy trial from Abeona this year, following allowance of an IND in February for ABO-102, for patients with MPS IIIA which commenced with dosing of the first cohort of patients in May.
- • On January 11, 2016, Abeona Therapeutics announced the Interministerial Council of Genetically Modified Organisms has approved the Genetically Modified Organism (GMO) Voluntary Release regulatory filings for Phase 1/2 Gene Therapy Clinical Study to treat patients with AB0-101 (AAV NAGLU) for patients with Sanfilippo syndrome type B (MPS IIIB). Additionally, the Comite Etico De Investigacion Clinica de Euskadi (CEIC-E) has approved the ethical committee regulatory filings for both ABO-101. The Company plans to file CTAs for the programs shortly for the upcoming clinical studies to be conducted at Cruces University Hospital (Bilbao, Spain).