CAR T-cell therapy shows encouraging early results in progressive MS
Most patients had stable or improved disability scores in small Phase 1 trial
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An experimental CAR T-cell therapy showed encouraging early results in a small Phase 1 trial involving people with progressive multiple sclerosis. (Image by iStock)
- The experimental CAR T-cell therapy azer-cel is being evaluated in a Phase 1 clinical trial for progressive multiple sclerosis.
- Participants had experienced worsening disability unrelated to relapses despite prior high-efficacy MS treatments.
- Early trial results showed stable or improved disability scores in most evaluable patients, with no dose-limiting toxicities or high-grade CAR T-cell-associated toxicities reported.
Most people with progressive forms of multiple sclerosis (MS) had stable or improved disability scores after receiving the experimental CAR T-cell therapy azercabtagene zapreleucel (azer-cel) in a small Phase 1 clinical trial.
TG Therapeutics, which is developing azer-cel under a licensing agreement with its previous developer, Precision Biosciences, presented the findings in a late-breaking oral session at MSToronto2026, the 10th joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, held last week in Toronto.
The presentation was titled “First Clinical Evaluation of an Allogeneic CD19-Directed CAR T-Cell Therapy in Progressive Multiple Sclerosis: Initial Results From the Phase 1 TG-Azercel-101 Study.”
CAR T-cell therapy targets B-cells in progressive MS
Progressive forms of MS include primary progressive (PPMS) and secondary progressive MS (SPMS). Both involve disability that gradually worsens over time, whether or not patients experience disease flares. Progressive MS has historically been harder to treat than relapsing forms of the disease.
Azer-cel is designed to deplete B-cells, immune cells that play a key role in MS. It uses T-cells, another type of immune cell, collected from healthy donors. These T-cells are modified to carry an engineered protein called a chimeric antigen receptor (CAR). The CAR directs them to target CD19, a protein found on B-cells. By removing B-cells, azer-cel aims to reduce the immune system’s attack on the nervous system that contributes to disability progression in MS.
TG is sponsoring a Phase 1 clinical trial (NCT06680037) of azer-cel in adults with several immune disorders involving B-cells, including relapsing and progressive forms of MS. The study is recruiting participants at eight sites across the U.S.
The analysis included 26 people with PPMS, active SPMS, or nonactive SPMS. All received azer-cel at doses ranging from 30 million to 500 million CAR T-cells. Before treatment, patients received bendamustine, a chemotherapy drug used to reduce their existing immune cells and make room for the CAR T-cells. This preparation is called lymphodepletion.
All 26 patients had experienced worsening disability unrelated to relapses during the previous year, despite treatment with high-efficacy MS medications. All had also previously received anti-CD20 therapies, which target B-cells. This class of MS treatments encompasses Ocrevus (ocrelizumab) and Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq), two therapies sold by Genentech that are currently the only approved treatments for PPMS in the U.S.
TG also markets an anti-CD20 therapy called Briumvi (ublituximab-xiiy), which is approved for relapsing forms of MS.
Most patients had stable or improved disability scores
Three months after a single infusion of azer-cel, 16 of 18 evaluable patients had stable or improved scores on the Expanded Disability Status Scale (EDSS), which measures overall physical disability. Three of those patients had improvements of at least two points on the EDSS, including one whose score improved by four points.
Of the eight patients evaluated at six months, seven had stable or improved EDSS scores, while one had worsening disability.
“These initial azer-cel results are particularly encouraging given that all patients entered the study with progressive disability despite prior treatment with high-efficacy therapies, including anti-CD20 treatment,” Michael S. Weiss, TG’s chairman and CEO, said in a company press release.
“Of particular interest, five of the 18 evaluable patients experienced improvements in disability scores, including three patients with improvements of two or more points on the EDSS scale, an encouraging early finding in a disease where even slowing progression can represent an important therapeutic advance,” Weiss said.
Early findings show B-cell depletion and encouraging safety results
At three months after azer-cel treatment, most evaluable patients also had stable or improved scores on tests measuring walking ability, hand dexterity, and cognitive processing speed. Tests also showed reduced B-cell counts in the blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord. According to TG Therapeutics, no dose-limiting toxicities or high-grade CAR T-cell-associated toxicities were observed in the study.
“The safety findings to date, together with evidence of B-cell depletion … demonstrate biological activity at doses that appear tolerable, while stable or improved disability scores in most subjects provide a potential signal of clinical activity,” Weiss said.
The researchers stressed that the findings are preliminary. Further research is ongoing to assess azer-cel’s long-term safety and effectiveness.
“While these results remain preliminary, we believe an off-the-shelf CAR T-cell therapy has the potential to offer a meaningful new treatment option for patients with progressive MS, where substantial unmet need remains. We look forward to continuing dose escalation and evaluating longer-term outcomes, and we are grateful to the patients, their families, and the clinical teams who are making this research possible,” Weiss said.
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