FDA Grants Orphan Drug Designation to Potential Treatment of STXBP1 Developmental and Epileptic Encephalopathy

Research that was carried out by Baylor College of Medicine and Texas Children’s Hospital doctors have led to the U.S. Food and Drug Administration (FDA) granting Orphan Drug Designation to a treatment for developmental and epileptic encephalopathy (DEE) due to syntaxin-binding protein 1 (STXBP1) mutations. The treatment was developed by Capsida Biotherapeutics and called CAP-002.  DEE caused by STXBP1 mutations is estimated to affect up to one in 26,000 children globally. It is associated with treatment-resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). 

“Receiving Orphan Drug Designation is an important milestone for our program, and for the patients and families affected by STXBP1 developmental and epileptic encephalopathy,” said Peter Anastasiou, Chief Executive Officer of Capsida Biotherapeutics. “There are no disease-modifying therapies available for this devastating disorder, and FDA’s granting ODD signals the significant potential that CAP-002 demonstrates based on non-clinical data.

CAP-002 is a novel, first-in-class IV-administered gene therapy designed to achieve brain-wide neuronal expression of the STXBP1 protein while significantly detargeting the liver. It is currently in IND-enabling studies. In adult mice lacking one functional copy of the STXBP1 gene, IV administration of the gene encoding STXBP1 rescues key phenotypic defects including seizures, motor deficits, and cognitive impairments, in a dose-dependent manner with long-lasting effects. Studies conducted by Capsida and Dr. Mingshan Xue, associate professor of neuroscience, molecular and human genetics at Baylor, as well as a member of the Cain Foundation Laboratories and the Duncan Neurological Research Institute at Texas Children’s Hospital, showed that the dose-dependent rescue of these neurological phenotypes was dependent on supplementation of STXBP1 in neurons throughout the brain and at levels not achievable by wild-type serotypes, such as AAV9.

“This milestone moves us one step closer to our goal of transforming the lives of people living with STXBP1 developmental and epileptic encephalopathy” said Swati Tole, M.D., Chief Medical Officer at Capsida. “We are committed to advancing CAP-002, with our IND filing in the first half of 2025, and bringing novel gene therapies to people with high unmet medical needs.”

The FDA’s Orphan Drug Designation is intended to encourage the development of treatments for rare diseases, defined as those affecting fewer than 200,000 people in the United States. ODD may shorten the clinical development path through closer FDA collaboration and potential qualification for expedited development programs.  This designation also provides the company with certain benefits, including tax credits for qualified clinical trials, exemption from user fees, and potential seven-year market exclusivity upon FDA approval.