Trial of CAR T-cell therapy for progressive MS now recruiting in US
It will test whether donor T-cells can target immune cells that drive inflammation
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A hand holds up a stethoscope, with the form of a person visible in the chestpiece of the medical device.
- A Phase 1 trial of azer-cel, a CAR T-cell therapy, for progressive multiple sclerosis is now recruiting.
- The therapy uses donor T-cells to destroy B-cells that drive multiple sclerosis inflammation.
- This trial of the "off-the-shelf" treatment aims to assess safety and impact on disability progression.
A Phase 1 clinical trial testing azercabtagene zapreleucel (azer-cel), TG Therapeutics’ CAR-T-cell therapy, in progressive forms of multiple sclerosis (MS) is now recruiting participants at eight sites across the U.S.
The study (NCT06680037) is expected to enroll up to 32 adults with primary progressive MS or secondary progressive MS to determine whether genetically engineered immune T-cells from healthy donors can safely and effectively improve patient outcomes. The first participant was dosed last year.
Under a licensing agreement, in which TG Therapeutics acquired the development and commercialization rights to azer-cel for autoimmune diseases, the trial’s advancement triggered a $7.5 million milestone payment to Precision Biosciences, which developed the therapy.
“We are pleased with TG Therapeutics’ continued advancement of azer-cel in progressive multiple sclerosis and with the achievement of this clinical milestone,” Michael Amoroso, Precision’s president and CEO, said in a company press release.
Azer-cel designed to eliminate disease-driving B-cells
MS is an autoimmune disease in which the immune system mistakenly attacks myelin, the protective coating surrounding nerve fibers, in the brain and spinal cord. Although multiple immune cell types are involved, B-cells are considered key drivers of disease activity.
Azer-cel is a type of CAR T-cell therapy designed to eliminate these disease-driving B-cells.
CAR T-cell therapies work by taking T-cells — a type of immune cell that normally helps fight infections — and genetically modifying them in the lab to produce a special receptor on their surface called a chimeric antigen receptor, or CAR. This receptor allows the T-cells to recognize and attach to a specific target.
In the case of azer-cel, the CAR is designed to recognize CD19, a protein found on the surface of B-cells. Once infused into the bloodstream, the engineered T-cells seek out and destroy B-cells, which is expected to reduce disease activity and slow disability accumulation.
Unlike most approved CAR T-cell therapies, which are made from a patient’s own T-cells, azer-cel is produced using T-cells from a healthy donor. This approach allows the therapy to be manufactured in advance as an “off-the-shelf” treatment, potentially making it more readily available to patients.
Importantly, the therapy has been engineered to reduce the risk of graft-versus-host disease, a complication of certain donor-derived treatments in which donor immune cells attack healthy tissues.
The ongoing Phase 1 trial is now testing several doses of azer-cel, given as a one-time infusion into the bloodstream. The main goal is to determine a recommended dose for future studies.
Secondary objectives include assessing safety, how the therapy behaves in the body, and potential effects on disability progression, brain lesions, and brain volume loss after up to two years. The trial is slated to conclude in 2029, but top-line results are expected later this year.
