The U.S. Food and Drug Administration granted its regenerative medicine advanced therapy (RMAT) designation to Abeona Therapeutics‘ investigative gene therapy ABO-102, under development for the treatment of Sanfilippo syndrome type A.
Also known as MPS IIIA (mucopolysaccharidosis type IIIA), Sanfilippo syndrome type A is a severe and progressive disorder caused by the toxic accumulation of heparan sulfate — a specific type of large sugar molecule called glycosaminoglycan (GAG).
The disease mainly affects the central nervous system (the brain and spinal cord), leading to progressive mental deterioration and behavioral changes such as aggression, hyperactivity, and sleep disturbances.
ABO-102 is a one-time adeno-associated virus (AAV)-based gene therapy designed to ease the delivery of the correct copy of the gene associated with the onset and progression of Sanfilippo syndrome type A. This gene works to break down and degrade heparin sulfate.
Preclinical efficacy studies in mice with the disease have shown functional benefits that are sustained for months to years after treatment.
A single dose of ABO-102 significantly restored normal cell and organ function, corrected cognitive defects, increased neuromuscular function, and normalized the lifespan of the engineered mice by over 100 percent for more than one year after treatment.
ABO-102’s safety and effectiveness is currently being evaluated in an ongoing, open-label, dose-escalation Phase 1/2 trial (NCT02716246). The study, which started in 2016, is still recruiting adults and children at least 6 months old with a confirmed diagnosis of Sanfilippo syndrome type A.
The trial’s estimated completion date is December 2020, with a primary completion date of December 2019. For more information, visit the clinical trial’s regulatory webpage here.
Patients are divided into three groups: low-dose, medium-dose, and high-dose, and administered a single intravenous injection of ABO-102.
Preliminary results have shown that ABO-102 has significant dose-dependent and time-dependent responses in biomarker levels, including a reduction of heparan sulfate in the cerebral spinal fluid (CSF) and urine.
Cognitive assessments show that ABO-102 stabilizes or improves cognitive function at six months in the medium-dose group and one year in the low-dose group.
Safety assessments also showed that ABO-102 is well-tolerated, with no serious adverse events reported. Patients treated with the gene therapy also showed a reduction in liver volume, a known hallmark of the disease.
Updated results from the trial are expected to be presented at the American Society for Gene and Cell Therapy (ASGCT) 21st Annual Meeting taking place May 16-19 in Chicago.
The FDA’s RMAT designation is an expedited program designed to advance investigative regenerative medicine products. These are defined by the FDA as “a cell therapy, therapeutic tissue engineering product, human cell and tissue product,” or any combination of these products or therapies.
RMAT status allows companies developing gene therapies and regenerative medications to work more closely with the FDA, and grants the benefits of an FDA breakthrough therapy designation.
“We are encouraged to have received the first gene therapy RMAT designation in [Sanfilippo syndrome type A] and look forward to further collaborating with the FDA to determine next steps in the development pathway for ABO-102,” Carsten Thiel, PhD, Abeona’s CEO, said in a press release.
“This action further reinforces the clinical significance in the data observed in the ongoing Phase 1/2 trial and the high unmet need for effective treatment options for patients suffering from Sanfilippo syndrome type A,” Thiel added.
ABO-102 has been granted orphan drug, rare pediatric disease, and fast track designations in the U.S., and orphan product designation in the European Union.