PRINCETON, N.J. — October 23, 2026
Bristol Myers Squibb (NYSE: BMY) announced interim safety and efficacy findings from the Phase 1 Breakfree-2 study evaluating investigational zolacabtagene autoleucel (zola-cel; BMS-986353), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in people with highly active relapsing multiple sclerosis (haRMS) and progressive multiple sclerosis (PMS). The results were presented at MSToronto 2026, the 10th Joint Meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS), in Toronto, Canada. The study enrolled 66 participants, including 30 with haRMS and 36 with PMS, who had ongoing disease activity or worsening disability despite prior disease-modifying therapies. Participants had received a median of two previous therapies. The primary endpoint was safety, with efficacy assessed as a secondary endpoint. Across the reported dose-level 2 (DL2) group, all 60 treated patients remained off disease-modifying therapies at the last follow-up, including nine with more than 12 months of follow-up. Among evaluable participants receiving DL2 with at least 26 weeks of follow-up, six of seven haRMS patients met no evidence of disease activity (NEDA) criteria at or beyond Week 26. All eight haRMS patients with evaluable EDSS assessments at this time point had stable or improved disability scores. Among participants with progressive MS, 22 of 24 (92%) showed stability or improvement in disability progression, and all 24 had no new MRI activity. The safety profile was generally consistent with previously reported Phase 1 findings, although cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and a fatal event of septic pneumonia were reported. The fatal event occurred after the data cutoff. These findings provide preliminary evidence of potential clinical activity following treatment with zola-cel, but the single-arm, dose-escalation study and limited follow-up do not establish long-term efficacy or the durability of treatment-free disease control.
Zola-Cel Investigates Immune Reset Through CD19-Directed CAR T Cells
Zola-cel is an investigational autologous CD19-directed CAR T-cell therapy designed to target B cells involved in immune-mediated disease. Unlike donor-derived allogeneic therapies, autologous CAR T-cell products are manufactured from a patient’s own T cells. In the Breakfree-2 study, cells are collected through apheresis, engineered using the company’s next-generation NEX-T manufacturing process, and infused after lymphodepletion. The process is designed to produce CAR T cells with stable vector integration and an early-differentiated phenotype before infusion. Bristol Myers Squibb is investigating whether this approach can produce an immune reset that changes the course of autoimmune neurological disease. In multiple sclerosis, immune activity contributes to inflammation and damage within the central nervous system, potentially resulting in relapses, new MRI lesions and accumulating disability. CD19-directed CAR T-cell therapy is being evaluated as a way to deplete targeted B-cell populations and potentially alter the underlying immune processes. In Breakfree-2, the company reported that all participants treated at DL2 remained off disease-modifying therapies at their last follow-up. This included nine patients followed for more than 12 months. Among evaluable participants, the results included NEDA criteria being met by six of seven haRMS patients, stable or improved EDSS scores in eight of eight haRMS patients, and stable or improved disability progression in 22 of 24 participants with PMS. All 24 evaluable PMS patients also had no new MRI activity. These findings are encouraging early observations, but the absence of a control group and the limited numbers of participants with longer follow-up make it difficult to determine the magnitude of treatment benefit. The results also do not establish whether patients will remain free of disease activity or avoid further treatment over the longer term. Bristol Myers Squibb described the findings as supporting the potential of immune reset for people living with relapsing and progressive forms of MS, while acknowledging the need for continued research.
Breakfree-2 Reports Safety Findings and a Fatal Infection
The Breakfree-2 study (NCT06220201) is a Phase 1, multicenter, single-arm, dose-escalation trial evaluating the safety and efficacy of zola-cel in autoimmune neurological diseases, including relapsing MS, progressive MS and refractory myasthenia gravis. The reported MS cohorts included 66 participants treated across the study. Safety was the primary endpoint, while secondary assessments included NEDA status, confirmed disability progression measured using the Expanded Disability Status Scale (EDSS), and pharmacokinetic outcomes. Overall, 28 of 66 participants (42.4%) experienced CRS. Most cases were Grade 1, affecting 36.4% of participants, while 6.1% experienced Grade 2 CRS. The reported CRS events resolved in a median of two days. ICANS occurred in five participants (7.6%), with most events classified as Grade 1 or Grade 2 and resolving in a median of two days. One participant with PMS experienced Grade 4 ICANS, which was managed with corticosteroids and anakinra and resolved within four days. Following the data cutoff, a participant with haRMS experienced a fatal event of septic pneumonia. After zola-cel infusion, the patient developed late-onset motor symptoms that were not classified as ICANS and did not resolve with intermittent corticosteroids and intravenous immunoglobulin. High-dose cyclophosphamide was subsequently administered, and the patient developed septic pneumonia and died the following day, 44 days after infusion. The company reported that no additional Grade 5 events had occurred across its autoimmune disease CAR T-cell programs, which included 190 patients treated in Phase 1 studies. The fatal infection underscores the importance of continued safety monitoring as cellular therapies are investigated in autoimmune conditions. The study remains ongoing, and further follow-up will be needed to characterize the frequency, severity and timing of adverse events, as well as the durability of clinical outcomes.
Advertisement
Bristol Myers Squibb Advances Cell Therapy Research in Autoimmune Disease
Multiple sclerosis is a chronic neurological disease that can cause relapses, progressive disability and changes in mobility, cognition and daily functioning. People with highly active relapsing disease or continued disability progression despite high-efficacy therapies may have limited treatment options, creating a need for approaches that address underlying immune mechanisms. The Breakfree-2 findings offer an early look at the potential of CD19-directed CAR T-cell therapy in this setting. The reported results include treatment-free follow-up for all participants in the DL2 group, stable or improved disability measures in evaluable patients, and no new MRI activity among the reported PMS subgroup. However, the findings remain preliminary, and larger controlled studies with longer follow-up will be required to determine whether zola-cel can provide durable disease control or alter long-term disability outcomes. Bristol Myers Squibb is a global biopharmaceutical company focused on discovering, developing and delivering medicines for serious diseases. Its cell therapy research spans established cancer applications and emerging areas, including autoimmune disease. The company also markets BRIUMVI (ublituximab-xiiy), a CD20-directed monoclonal antibody approved in the United States for adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. BRIUMVI is a distinct therapy and should not be confused with investigational zola-cel. The company continues to evaluate cellular therapies as potential approaches to immune-mediated disease, with Breakfree-2 providing initial clinical data in relapsing and progressive MS. Further dose escalation, extended follow-up and additional clinical studies will be needed to clarify zola-cel’s benefit-risk profile and determine its potential place in treatment.
Source:Bristol Myers Squibb,Press release
