NEW YORK, N.Y. — October 23, 2026
TG Therapeutics (NASDAQ: TGTX) announced initial Phase 1 results for azercabtagene zapreleucel (azer-cel), an investigational allogeneic CD19-directed chimeric antigen receptor (CAR) T-cell therapy being evaluated in people with progressive multiple sclerosis (MS). The findings were presented 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 (ACTRIMS-ECTRIMS), held October 21–23 in Toronto, Canada. The study represents the first reported clinical evaluation of an allogeneic CD19-directed CAR T-cell therapy in progressive MS. Among participants with evaluable disability assessments, 89% (16 of 18) had stable or improved Expanded Disability Status Scale (EDSS) scores at Day 90, while 88% (7 of 8) maintained stable or improved scores at Day 180. Three participants experienced EDSS improvements of at least two points by Day 90, including one participant with a four-point improvement. The initial findings also showed evidence of B-cell depletion in peripheral blood and cerebrospinal fluid (CSF), supporting biological activity at the doses evaluated. TG Therapeutics reported an encouraging preliminary safety profile across six dose levels, with no dose-limiting toxicities or specified high-grade CAR T-associated toxicities observed. The study included 26 participants who had experienced progression despite prior treatment with high-efficacy disease-modifying therapies, including anti-CD20 treatment. The median baseline EDSS score was 6.0, indicating substantial disability. The data cutoff was September 3, 2026, with a median follow-up of 4.9 months. The company emphasized that these results remain preliminary and that dose escalation and longer-term follow-up are continuing. While the findings provide early evidence of biological activity and possible clinical effects, the small study population and limited follow-up mean that the therapy’s efficacy and long-term safety have not yet been established.
Azer-Cel Targets CD19-Positive B Cells Through CAR T-Cell Therapy
Azer-cel is an investigational allogeneic CAR T-cell therapy designed to target CD19-positive B cells. Unlike autologous CAR T-cell therapies, which are manufactured using an individual patient’s own cells, an allogeneic approach uses donor-derived cells and is being developed with the potential to provide an off-the-shelf treatment option. The therapy is being evaluated in progressive multiple sclerosis, a condition in which neurological disability can accumulate over time, sometimes despite treatment with high-efficacy disease-modifying therapies. B cells are involved in immune processes that contribute to MS, and targeting them is an established therapeutic strategy in the disease. Azer-cel is designed to use engineered T cells to target CD19-positive B cells, potentially affecting B-cell populations beyond those addressed by therapies targeting CD20. In the Phase 1 study, peripheral blood B-cell counts fell below 10 cells/µL in 96% of participants (25 of 26). CSF samples from 21 participants showed a median reduction of 52.3% in CD19-positive B-cell events at Day 10. B-cell reconstitution was observed as early as Day 42 and favored transitional and naïve B-cell populations. These findings demonstrate measurable biological activity in the compartments assessed, although their relationship to sustained clinical benefit requires further study. TG Therapeutics Chairman and Chief Executive Officer Michael S. Weiss said the findings were encouraging because participants had experienced progressive disability despite prior high-efficacy treatments, including anti-CD20 therapy. He highlighted the combination of preliminary safety findings, B-cell depletion in blood and CSF, and stable or improved disability scores in most evaluable participants. The company believes an off-the-shelf CAR T-cell approach could potentially offer a new option for progressive MS, where significant unmet medical needs remain. However, the results do not yet establish whether azer-cel can slow long-term progression, reverse disability consistently or provide durable benefit.
Phase 1 Study Reports Safety and Functional Assessments
The TG-Azercel-101 Phase 1 study evaluated 26 participants with progressive MS across six azer-cel dose levels, ranging from 30 million to 500 million CAR T cells, following bendamustine lymphodepletion. All participants had experienced progression independent of relapse activity (PIRA) within the 12 months before enrollment despite high-efficacy disease-modifying treatment, and all had previously received anti-CD20 therapy. The median baseline EDSS score was 6.0. At the September 3, 2026 data cutoff, median follow-up was 4.9 months, with a range of 0.1 to 15 months. The initial safety findings included no dose-limiting toxicities, no Grade 3 or higher cytokine release syndrome (CRS), no Grade 2 or higher immune effector cell-associated neurotoxicity syndrome (ICANS), no graft-versus-host disease, no immune effector cell-associated hemophagocytic syndrome (IEC-HS), and no Grade 3 or higher infections. The company reported no high-grade CAR T-associated toxicities within these specified categories. Functional assessments at Day 90 showed that 94% of evaluable participants had stable or improved walking performance (16 of 17), 94% had stable or improved upper-extremity function (17 of 18), and 78% had stable or improved cognitive processing speed (14 of 18). MRI assessments found no gadolinium-enhancing T1 lesions or new or enlarging T2 lesions among the 22 participants evaluable by MRI. These observations provide additional early information about clinical status during treatment, but they should be interpreted cautiously given the study’s open-label design, small sample size and limited follow-up. The ongoing dose-escalation study will continue to evaluate safety, tolerability, biological activity and longer-term disability outcomes. Additional data will be needed to determine whether the observed changes are sustained and how they compare with the natural course of progressive MS.
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TG Therapeutics Advances Research in B-Cell Diseases
Progressive multiple sclerosis can lead to increasing mobility limitations, reduced independence and other neurological impairments. Although approved therapies are available for relapsing forms of MS and some active progressive disease, people with continued disability accumulation despite high-efficacy treatment remain an important research population. Azer-cel is being investigated as a potential new approach using engineered donor-derived T cells to target CD19-positive B cells. Its initial Phase 1 findings include substantial peripheral B-cell depletion, a reduction in CSF CD19-positive B-cell events, and stable or improved disability scores in most participants with available assessments at Day 90 and Day 180. The preliminary safety results also provide an early basis for continued evaluation, although longer follow-up and larger studies are necessary to characterize less common or delayed adverse events. TG Therapeutics is a fully integrated, commercial-stage biotechnology company focused on developing and commercializing treatments for B-cell diseases. Its portfolio includes BRIUMVI (ublituximab-xiiy), an approved anti-CD20 monoclonal antibody for adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. BRIUMVI is a separate therapy from investigational azer-cel, and its approved indications should not be interpreted as approval of azer-cel for progressive MS. The company continues to advance its research pipeline while evaluating the potential of cellular therapies in areas with unmet medical needs. The current azer-cel findings are an initial clinical signal rather than definitive evidence of efficacy. Continued dose escalation, longer-term follow-up and further clinical evaluation will be necessary to establish the therapy’s benefit-risk profile and potential role in progressive multiple sclerosis.
Source:TG Therapeutics,Press release
