Capsida Biotherapeutics Pauses Gene Therapy Trial Following Patient Death

Capsida Biotherapeutics, a California-based biotech company, has voluntarily paused its phase 1/2 clinical trial for CAP-002, a gene therapy targeting STXBP1 encephalopathy, following the death of the first patient enrolled in the study. The company is now working to determine the root cause of this tragic event, which has sent ripples through the gene therapy community and raised questions about the safety of novel delivery methods.

Trial Suspension and Immediate Response

The SYNRGY study, which began in July 2025, was designed to evaluate CAP-002 in children aged 18 months to seven years with STXBP1 encephalopathy, a condition characterized by abnormal brain function and recurrent seizures. Capsida announced the trial's suspension in a letter addressed to the STXBP1 community, acknowledging the devastating nature of the news and promising to work with urgency to gather information and find answers.

"We have voluntarily paused the CAP-002 SYNRGY study while we determine the root cause of the patient's passing," Capsida stated. The company has alerted the FDA and plans to provide a full report in compliance with regulations. The next steps for this program will be assessed once the investigation is complete.

Innovative Delivery Technology and Pre-Clinical Promise

CAP-002 was developed using Capsida's proprietary adeno-associated virus (AAV) capsid engineering platform. The therapy was designed to "detarget" the liver and dorsal root ganglia while effectively crossing the blood-brain barrier, a feature that Capsida had hailed as a breakthrough in intravenous delivery for gene therapies.

The company's approach involves screening capsid candidates in nonhuman primates to identify those that target desired tissues and cells while avoiding undesired tissues. This method was intended to overcome safety concerns associated with other gene therapies, particularly off-target effects in the liver and immune responses following intravenous administration.

Preclinical toxicology studies had suggested a well-tolerated safety profile for CAP-002, raising expectations for its performance in human trials. The sudden setback underscores the unpredictable nature of translating preclinical success to human subjects, especially in the complex field of gene therapy.

Industry Implications and Partnerships

The trial suspension comes at a critical time for Capsida, which has garnered significant attention and partnerships within the pharmaceutical industry. The company has ongoing collaborations with major players such as AbbVie, CRISPR Therapeutics, and Eli Lilly. In January, AbbVie exercised a $40 million option to advance a Capsida-partnered CNS gene therapy, highlighting the industry's confidence in the company's technology.

Capsida's platform has also attracted interest beyond STXBP1 encephalopathy, with programs in development for Parkinson's disease and Friedreich's ataxia. The company initiated a clinical trial for its Parkinson's program just last month, adding to the stakes of the current investigation.

As Capsida works to unravel the circumstances surrounding the patient death in the CAP-002 trial, the broader gene therapy field will be watching closely. The outcome of this investigation could have far-reaching implications for the development and regulation of novel gene therapy delivery methods, potentially influencing the trajectory of numerous ongoing and planned clinical studies across the industry.