Patient Death in Gene Therapy Trial Halts Capsida's Clinical Study

Capsida Biotherapeutics has suspended its clinical trial for an experimental gene therapy following the death of the first participant treated in the study. The biotechnology company is now investigating the root cause of this devastating event, which has sent ripples through the pharmaceutical industry and raised concerns about the safety of gene therapies.

Trial Suspension and FDA Notification

Capsida disclosed the patient death in a letter to the STXBP1 disorder community on Wednesday. The company has voluntarily paused the study and informed the U.S. Food and Drug Administration (FDA) about the incident. Capsida CEO Peter Anastasiou stated, "We are working with the appropriate parties and will share information with the medical and patient communities as soon as we can."

The trial, which began just four months ago in May, was testing CAP-002, a gene therapy designed to treat developmental and epileptic encephalopathy related to mutations in the syntaxin-binding protein 1 (STXBP1) gene. The study aimed to enroll approximately 12 children with STXBP1-related disorders at Weill Cornell Medicine in New York and the Children's Hospital of Philadelphia.

STXBP1 Disorders and CAP-002

STXBP1-related disorders typically manifest with seizures in the first year of life, along with developmental delays, decreased muscle tone, and difficulties in walking and speaking. The condition also carries a risk of sudden death in epilepsy. CAP-002, administered intravenously, was developed to provide a stable supply of the STXBP1 protein throughout the brain, addressing the deficiency caused by gene mutations.

Capsida's approach involved custom-designing a viral vector to effectively deliver the therapy to brain neurons, as naturally occurring viruses commonly used in gene therapies do not adequately penetrate this area. The company had previously claimed that CAP-002 possessed a "superior safety profile" compared to other gene therapies due to its targeted approach.

Industry-wide Concerns

This incident follows a series of patient deaths in gene therapy trials over the past year, including two linked to Sarepta Therapeutics' Duchenne muscular dystrophy treatment Elevidys and another associated with a limb-girdle muscular dystrophy therapy. These events have intensified scrutiny of gene therapies across the pharmaceutical industry.

Other recent patient deaths in clinical trials include:

• Allogene Therapeutics' discontinuation of ALLO-647, a monoclonal antibody used for lymphodepletion, after a mortality in a Phase II CAR T therapy study.
• CytomX's report of a death in an early-stage study for an investigational antibody-drug conjugate for colorectal cancer.
• Agios Pharmaceuticals' disclosure of three deaths in July among patients treated with its approved anemia drug Pyrukynd.

As the industry grapples with these setbacks, the focus on patient safety in gene therapy trials is likely to intensify, potentially impacting the development timelines and regulatory pathways for these cutting-edge treatments.