Early trial of experimental CAR T-cell therapy seeks people with NMOSD
Study open to adults with other autoimmune conditions affecting nervous system
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CRISPR Therapeutics has launched a Phase 1 clinical trial to test its experimental cell therapy zugocabtagene geleucel (zugo-cel) in adults with relapsing neuromyelitis optica spectrum disorder (NMOSD), which means the disease is flaring.
The Phase 1 study (NCT07804004) is also open to adults with other autoimmune conditions that affect the nervous system, including progressive multiple sclerosis, myelin oligodendrocyte glycoprotein antibody-associated disease, and stiff person syndrome. Enrollment is ongoing globally, according to a press release from CRISPR, even though specific site locations have not yet been disclosed.
Zugo-cel targets key protein
NMOSD is a rare autoimmune disorder in which the immune system launches an attack that targets healthy cells in the brain and spinal cord. This autoimmune attack is driven in most cases by self-reactive antibodies that target aquaporin-4 (AQP4), a protein highly present in nerve-supporting cells in the brain.
Antibodies, including the anti-AQP4 antibodies that drive NMOSD, are produced by immune cells called B-cells. Zugo-cel, formerly known as CTX112, is designed to kill B-cells, thereby reducing levels of disease-driving antibodies and ultimately reducing disease activity.
Zugo-cel belongs to a class of treatments called CAR T-cell therapies, which take advantage of T-cells, a type of immune cell that is able to kill other cells. With CAR T-cell therapies, these immune cells are modified in the lab to carry a human-made protein called a chimeric antigen receptor (CAR), which acts like a wanted poster directing the killer cells to attack a specific target. In Zugo-cel, the CAR protein targets CD19, a protein present at the surface of B-cells.
Traditional CAR T-cell therapies use a patient’s own T-cells. This requires the time-consuming and expensive process of collecting a patient’s T-cells, taking them to a lab to modify them, and then returning them to the patient.
By contrast, zugo-cel is an off-the-shelf CAR T-cell therapy, meaning that it uses T-cells that are collected from a healthy donor and prepared in advance to be administered whenever needed, which can cut down on costs and time.
Trial will evaluate therapy’s safety profile
In the new Phase 1 trial, participants will initially undergo lymphodepleting chemotherapy, a treatment regimen that aims to kill a patient’s existing immune cells to make room for the therapeutic cells. They will then receive one-time treatment with zugo-cel, given by infusion into the bloodstream.
The trial’s main goal is to evaluate the experimental therapy’s safety profile over the course of a month following administration. Secondary goals include assessing zugo-cel’s pharmacological properties and preliminary efficacy up to two years after infusion.
Zugo-cel is also being evaluated in two other ongoing Phase 1 trials: one focused on blood-related autoimmune conditions, and the other focused on body-wide autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis.
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