Bristol Myers details CAR T trial death, data

BMY shares slip after death in MS CAR T trial

Shares of Bristol Myers Squibb (BMY) fell 2% on Friday after the company disclosed that a patient died in its early-stage Breakfree-2 study of the investigational CAR T cell therapy zolacabtagene autoleucel, or zola-cel, in multiple sclerosis. The fatal event involved a patient with highly active relapsing multiple sclerosis who developed septic pneumonia and died 44 days after receiving the zola-cel infusion.

The patient had experienced late-onset motor symptoms that were not attributed to immune effector cell-associated neurotoxicity syndrome and did not improve with intermittent corticosteroids or intravenous immunoglobulin. Doctors then administered a high-dose or potent immunosuppressant drug, after which the patient developed septic pneumonia and died the following day.

Details of the Breakfree-2 Phase 1 study

Breakfree-2 is a single-arm, dose-escalation Phase 1 trial evaluating zola-cel, an autologous CD19-directed CAR T cell therapy, in patients with highly active relapsing and progressive forms of multiple sclerosis. The study enrolled 66 patients who had ongoing disease activity or worsening disability despite prior treatments, including 30 with highly active relapsing MS and 36 with progressive forms of MS.

Patients in the study had a median of two prior disease-modifying therapies. The primary endpoint of Breakfree-2 is safety, with efficacy as a secondary endpoint. Bristol Myers reported that all 60 patients treated at dose level 2 remained off disease-modifying therapies at last follow-up, including nine patients who had been followed for more than 12 months.

Reported safety profile and adverse events

Interim data released on October 23 indicated that zola-cel showed a safety profile consistent with previously reported Phase 1 data. Most adverse events in the multiple sclerosis cohorts were brief and reversible. Cytokine release syndrome occurred in 42.4% of the 66 patients, with most events classified as Grade 1, and all cytokine release cases resolving in a median of two days.

Immune effector cell-associated neurotoxicity syndrome occurred in 7.6% of patients, with most ICANS events classified as Grade 1 or 2 and resolving in a median of two days. One Grade 4 ICANS event was reported in a patient with progressive MS; this life-threatening event was managed with corticosteroids and anakinra and resolved within four days.

The fatal septic pneumonia case occurred after the study’s interim data cutoff. Bristol Myers stated that no additional Grade 5 events have been reported across its zola-cel programs in autoimmune diseases, which include 190 patients treated in Phase 1 studies. A company spokesperson said the death occurred after Bristol Myers had already decided to pause enrollment in the program.

Early efficacy signals in multiple sclerosis

Among evaluable patients treated at dose level 2 with at least 26 weeks of follow-up, early efficacy signals were reported. Six of seven patients with highly active relapsing MS met criteria for no evidence of disease activity. All eight evaluable relapsing MS patients at this dose level demonstrated stability or improvement on the Expanded Disability Status Scale.

In the progressive MS group, 22 of 24 evaluable patients showed stability or improvement in disability progression, with no new lesions detected on MRI scans. Bristol Myers characterized these findings as early and promising efficacy across both highly active relapsing and progressive MS populations in the study.

Broader safety scrutiny in autoimmune CAR T research

Safety concerns around CAR T therapies for autoimmune conditions have increased as more safety events have emerged. In late August, Bristol Myers voluntarily paused some autoimmune trials of zola-cel after identifying safety signals and observing transient and reversible inflammatory events during routine study surveillance.

Around the same period, Novartis (NVS) suspended multiple CAR T autoimmune studies after three patients who received its therapy died following an overactive immune condition. Bristol Myers’ latest disclosure of a septic pneumonia death in its multiple sclerosis trial adds to the broader reassessment of risk in developing CAR T therapies for non-oncologic autoimmune diseases.