Topline Findings
- SYNRGY trial paused: Capsida Biotherapeutics has voluntarily paused the CAP-002 gene therapy trial for STXBP1-related disorders following the death of the first enrolled patient, while investigating the cause with the FDA.
- Promising preclinical results: Preclinical studies showed over 70% neuronal transduction and a tolerable safety profile, making CAP-002 a first-in-human, intravenous, blood–brain barrier-crossing gene therapy.
- STXBP1 prevalence and mortality: STXBP1 developmental and epileptic encephalopathy affects roughly one in 26,000–30,000 births, with a 3.2% mortality rate and sudden unexpected death in epilepsy as the leading cause of death.
Capsida Biotherapeutics announced that the first patient enrolled in its SYNRGY trial for CAP-002 in STXBP1-related disorders has died, prompting the company to voluntarily pause the trial. According to the company, it is working urgently with external experts and the FDA to investigate the cause of the patient’s death, ensure the safety of other patients enrolled in the trial, and determine next steps for the program while maintaining transparent communication with the STXBP1 community.1
What Factors Could Influence the Future of the CAP-002 SYNRGY Trial?
“We understand this devastating news will raise questions and uncertainty, and we are working with urgency to gather information and find answers” the company stated in a letter. “We have voluntarily paused the CAP-002 SYNRGY study while we determine the root cause of the patient’s passing. As we continue to work closely with our partners and relevant experts, we have alerted the FDA and will be providing them with a full report in compliance with regulations. Once this work is complete, we can begin to assess next steps with respect to this important program.”
Preclinical Data and Regulatory Context
The voluntary pause of Capsida Biotherapeutics’ CAP-002 gene therapy trial comes just months after the FDA cleared the company’s Investigational New Drug (IND) application, marking a sudden and unexpected halt in the development of what had been considered a potentially groundbreaking treatment for STXBP1-related disorders. The treatment was also granted Fast Track designation in the same month.2,3
- The IND, which was first announced in May, was based on results from preclinical studies in non-human primates.
- The results demonstrated robust and widespread neuronal transduction, with more than 70% of neurons across critical brain regions expressing the therapeutic STXBP1 gene.
- Additionally, GLP toxicology studies indicated a tolerable safety profile, with no adverse histopathology observed.
- According to Capsida, this is the first program entering a human clinical trial utilizing an intravenously administered, blood brain barrier-crossing, engineered capsid that also is detargeted from off-target tissues.2
“STXBP1-related disorders present devastating challenges in communication, development, motor function and seizures,” said Charlene Son Rigby, STXBP1 Foundation president, co-founder, in a press release. “We are in dire need of targeted therapies that can improve the lives and functioning of our children and families.”2
STXBP1 Developmental and Epileptic Encephalopathy Prevalence and Mortality
- According to Capsida, STXBP1 developmental and epileptic encephalopathy is estimated to occur in roughly one in 26,000 births globally, affecting approximately 5,000 children across the United States and Europe.1
- A recent study found that the updated incidence rate for STXBP1 mutations is approximately 3.3 to 3.8 children per 100,000 births, which translates to one in 26,000 to one in 30,000 births.4
- Results from an October 2024 study published in Neurological Sciences showed a mortality rate of 3.2% for patients with pathogenic STXBP1 variants.
- Detailed review of 40 cases from multiple centers worldwide showed a median age at death of 13 years, ranging from 11 months to 46 years.
- The leading cause of death was sudden unexpected death in epilepsy (SUDEP), accounting for 36% of cases, followed by pulmonary infections and respiratory complications at 33%.
- SUDEP incidence peaked in mid-childhood, whereas non-SUDEP causes were more common in early childhood and adulthood.5
“We are committed to keeping the community informed about what happened and our plans for the program as soon as we have information to share,” the letter concluded. “We understand that a letter will not ease the pain you are all feeling, but we want you to know we are mourning together with the patient’s family and all of you. We are committed to timely and transparent communication with the STXBP1 community.”
References
- A Letter to the STXBP1 Community. Capsida. September 10, 2025. Accessed September 12, 2025. https://capsida.com/a-letter-to-the-stxbp1-community/
- Capsida Receives FDA IND Clearance for Its First-in-Class, IV-administered Gene Therapy for STXBP1 Developmental and Epileptic Encephalopathy. Capsida. May 12, 2025. Accessed September 12, 2025. https://capsida.com/capsida-receives-fda-ind-clearance-for-its-first-in-class-iv-administered-gene-therapy-for-stxbp1-developmental-and-epileptic-encephalopathy/
- Capsida Receives FDA Fast Track Designation for Its Potential First-in-Class IV-Administered Gene Therapy for STXBP1 Developmental and Epileptic Encephalopathy. Capsida. May 29, 2025. Accessed September 12, 2025. https://capsida.com/capsida-receives-fda-fast-track-designation-for-its-potential-first-in-class-iv-administered-gene-therapy-for-stxbp1-developmental-and-epileptic-encephalopathy/?utm_source=chatgpt.com
