Bristol Myers Squibb reports Phase 1 zola-cel results in multiple sclerosis, including disability stability, MRI findings and safety events.
Written By: Aasritha Thippavajjala,
PharmD
Reviewed By: Pharmacally Editorial Team
Bristol Myers Squibb (BMS) has reported interim safety and efficacy findings from the Phase 1 Breakfree-2 study of zolacabtagene autoleucel (zola-cel; BMS-986353), an investigational autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy for multiple sclerosis (MS). The results were presented on October 23, 2026, at MSToronto 2026, the 10th Joint ACTRIMS-ECTRIMS Meeting. The findings provide preliminary evidence of disease control in relapsing and progressive MS, although the small, uncontrolled efficacy analyses and reported safety events warrant cautious interpretation.
Study Design and Patient Population
Breakfree-2 (NCT06220201) is a multicentre, single-arm, dose-escalation Phase 1 study evaluating zola-cel in patients with autoimmune neurological diseases, including highly active relapsing MS (haRMS), progressive MS (PMS) and refractory myasthenia gravis. The reported analysis covered the MS cohorts.
The study included 66 patients: 30 with haRMS and 36 with PMS. Participants had ongoing disease activity or worsening disability despite previous treatment and had received a median of two disease-modifying therapies (DMTs). Previous DMT exposure ranged from one to eight therapies in haRMS and one to six in PMS. Safety was the primary endpoint, while efficacy was assessed as a secondary endpoint.
Zola-cel is manufactured using BMS’s NEX-T platform. The treatment process involves collecting patients’ T cells through apheresis, engineering them into CD19-directed CAR T cells, administering lymphodepleting chemotherapy and delivering a single infusion. The approach is intended to deplete B cells and potentially reset immune activity, but its long-term clinical effects remain under investigation.
Interim Efficacy Findings in Relapsing and Progressive MS
All 60 patients treated at dose level 2 (DL2) remained off DMTs at their last follow-up, including nine patients followed for more than 12 months. This observation indicates that additional DMT treatment had not been resumed at the reported assessments, but does not establish sustained treatment-free remission or durable disease control.
Among 32 evaluable DL2 patients with at least 26 weeks of follow-up, six of seven patients with haRMS assessed for no evidence of disease activity (NEDA) met the criteria. NEDA required the absence of relapses, disability progression and MRI activity. All eight evaluable haRMS patients assessed using the Expanded Disability Status Scale (EDSS) showed stable or improved scores.
In the PMS group, 22 of 24 evaluable patients (92%) demonstrated stability or improvement in disability progression, despite worsening disability at baseline. All 24 patients had no new MRI activity at the reported assessment.
These findings suggest potential disease control across both MS populations. However, the endpoint-specific analyses involved small subsets of patients, and the single-arm study cannot determine whether the observed outcomes are attributable to zola-cel beyond what might have occurred with other treatment strategies or over the same period without treatment.
Safety Findings Include CRS, ICANS and a Fatal Event
Cytokine release syndrome (CRS) occurred in 28 of 66 patients (42.4%). Most cases were Grade 1 (36.4% of the overall study population), while 6.1% were Grade 2. All CRS events resolved, with a median resolution time of two days.
Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in five patients (7.6%). Most cases were Grade 1 or 2 and resolved within a median of two days. One patient with PMS experienced Grade 4 ICANS, which resolved within four days following treatment with corticosteroids and anakinra.
BMS also reported a fatal case of septic pneumonia after the data cutoff. A patient with haRMS 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. The patient developed septic pneumonia and died the following day, 44 days after zola-cel infusion.
The announcement does not establish the causal relationship between zola-cel and the fatal event. BMS reported no additional Grade 5 events across its autoimmune-disease zola-cel programmes, which included 190 patients treated in Phase 1 studies.
Clinical Interpretation
Breakfree-2 provides an early signal that CD19-directed CAR T-cell therapy may help control disease activity and stabilise disability in some patients with relapsing or progressive MS. The absence of new MRI activity in the evaluable PMS group and the proportion showing stable or improved disability are notable given the reported worsening at baseline despite previous treatment.
However, these findings do not yet establish durable disease modification or superiority over approved MS therapies. Remaining off DMTs is not equivalent to demonstrating sustained remission, and the efficacy results apply to specific evaluable subgroups rather than all enrolled patients.
The CRS and ICANS events, together with the fatal septic pneumonia case, also highlight the importance of continued safety evaluation. Larger studies with longer follow-up are needed to establish the durability of clinical benefit, identify relevant risks and determine the overall benefit-risk profile of zola-cel in MS.
Reference
Bristol Myers Squibb Presents Results from Phase 1 Breakfree-2 Study of Zolacabtagene Autoleucel (BMS-986353) in Patients with Highly Active Relapsing and Progressive Forms of Multiple Sclerosis at MSToronto 2026, Bristol Myers Squibb, 23 October 2026
A Study to Evaluate the Safety, Tolerability, Efficacy, and Drug Levels of CC-97540 in Participants with Relapsing Forms of Multiple Sclerosis, Progressive Forms of Multiple Sclerosis or Refractory Myasthenia Gravis (MG) (Breakfree-2), ClinicalTrials.gov ID NCT06220201
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.