CAR T-cell therapy trial for progressive MS now recruiting; stem cell transplant trials advance

A Phase 1 clinical trial testing azercabtagene zapreleucel (azer-cel), TG Therapeutics' CAR-T-cell therapy, in progressive forms of multiple sclerosis is now recruiting participants at eight sites across the U.S. The study 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.

Azer-cel is a type of CAR T-cell therapy designed to eliminate disease-driving B-cells. The therapy works by taking T-cells and genetically modifying them in the lab to produce a chimeric antigen receptor, or CAR, on their surface. This receptor allows the T-cells to recognize and attach to 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. 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 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.

The ongoing Phase 1 trial is 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.

In parallel developments, multiple randomized trials are now underway that will directly compare hematopoietic stem cell transplantation against the most effective disease-modifying therapies. This represents a critical step, because it moves transplant from anecdote and observational data into true evidence-based positioning within the MS treatment algorithm.

Over the past decade, hematopoietic stem cell transplantation and other cell-based therapies have moved from the margins of MS research into the center of high-level scientific debate. As high-efficacy disease-modifying therapies have reshaped inflammatory control in relapsing MS, attention has increasingly turned to whether more aggressive immune reconstitution strategies can deliver deeper, more durable remission.