Emerging treatmentsResults from peopleOne death and early observations; benefit unproven

Interim human results from a Phase 1 study with one treatment group and no comparison group

Zola-cel: one death and early observations in a Phase 1 CAR-T study in 66 people with MS

Published by MyelinWatch: 5 Nov 2026

Organisation: Bristol Myers Squibb · United States
Study sponsor: Juno Therapeutics, a Bristol Myers Squibb company
Researcher: Jeffrey A. Cohen and colleagues

What happened

On 23 October 2026, Bristol Myers Squibb reported interim results from the Phase 1 Breakfree-2 study of zola-cel, an experimental CD19-directed CAR T-cell therapy made from a person's own cells and given as a single infusion. One person with highly active relapsing multiple sclerosis (MS) died of septic pneumonia 44 days after the infusion. The death happened after the data cutoff. This person had late-onset motor symptoms, described as non-ICANS, that did not resolve with corticosteroids and intravenous immunoglobulin, received high-dose cyclophosphamide, developed septic pneumonia and died the following day. The study has no comparison group. It included 66 people: 30 with highly active relapsing MS and 36 with progressive MS. Cytokine release syndrome occurred in 28/66 and the neurotoxicity syndrome ICANS in 5/66, including one Grade 4 event that resolved within four days. Among people who received the main dose and had at least 26 weeks of follow-up, 22 of 24 with progressive MS were reported as stable or improved on disability and all 24 had no new MRI activity. In highly active relapsing MS, 6 of 7 evaluable people had no evidence of disease activity.

What this means for people with MS

Without a comparison group, these observations cannot show that zola-cel caused the stability seen, and they cannot show that it slows disability. Follow-up is short: among the 60 people who received the main dose, the company reports nine with more than 12 months. The reported cause of death was septic pneumonia; how zola-cel and the treatment that followed contributed remains unresolved. A company spokesperson told Reuters that other complications and heavy prior treatment confound finding the root cause, as quoted by Pharmaceutical Executive. The presenter, Jeffrey Cohen, said the death was presumed to be in some way related to the CAR-T therapy, as reported by Healio. Pharmaceutical Executive also reported that the company paused zola-cel studies in September 2026 and aims to resume enrolment in early 2027; the company release does not mention this. Zola-cel is experimental and is not an available MS treatment.

What kind of evidence exists?: Bristol Myers Squibb announcement of interim conference results; single-arm Phase 1 study, not peer reviewed
How reliable is this source?: Primary company announcement of interim conference results, not peer-reviewed; the conference abstract was not read. Quoted statements on the cause of death come from specialist news reports. Healio reports 57 participants, while the company release reports 66; the figure here follows the company release.

Source: Bristol Myers Squibb — official company announcement ↗Source: ClinicalTrials.gov — Breakfree-2, NCT06220201 ↗ Source: Healio — report of the presentation, 2 November 2026 ↗ Source: Pharmaceutical Executive — report on the death and the study pause, 26 October 2026 ↗

Research event/source date: 23 Oct 2026
Published by MyelinWatch: 5 Nov 2026
Last substantive MyelinWatch update: 5 Nov 2026

Related substantive developments

Research event/source date: 2 Nov 2026

Emerging treatmentsRegistered study in peopleStudy authorised in Greece; not a result

Phase 3 extension study authorised in Greece; recruitment not yet started

Frexalimab: Greece authorises the long-term Phase 3 extension study

Organisation: Sanofi · France

The EU Clinical Trials Information System (CTIS) shows that Greece authorised Sanofi's Phase 3 extension study LTS18002 (2026-525688-41-00) on 2 November 2026. Denmark, Portugal and Poland authorised it on the same day, after Belgium (30 October 2026) and Austria (1 November 2026); all six countries are listed as authorised with recruitment pending. The record plans 17 participants in Greece and lists four Greek hospitals: AHEPA University General Hospital of Thessaloniki, the University General Hospital of Ioannina, the General University Hospital of Larissa and the 401 General Military Hospital of Athens. The study will look at the long-term safety and tolerability of frexalimab, an experimental antibody, in people with multiple sclerosis (MS). It is open only to people who complete earlier frexalimab studies on the study drug, such as the Phase 3 studies FREXALT and FREVIVA. The estimated EU recruitment start is 15 February 2027.

Published by MyelinWatch: 3 Nov 2026

What this means for people with MS

Authorisation means the study may proceed in Greece; it does not mean that it has started at any Greek hospital, that anyone has received treatment in it, or that frexalimab works. No Phase 3 results are available yet. People who are not already in a frexalimab study cannot join this extension, so it is not a way for other people with MS in Greece to receive frexalimab. Frexalimab is not an available treatment in Greece.

Read the update →Source: EU Clinical Trials Information System (CTIS), European Medicines Agency — official CTIS record ↗Source: ClinicalTrials.gov — FREXALT (NCT06141473), Phase 3, ongoing, not accepting new participants ↗ Source: ClinicalTrials.gov — FREVIVA (NCT06141486), Phase 3, ongoing, not accepting new participants ↗

Research event/source date: 30 Oct 2026

Emerging treatmentsResults from peopleDescriptive observations; causality unproven

Published observational follow-up of 204 people with relapsing MS in Italy and Switzerland, without a comparison group

CladStop: almost four years of follow-up after the two-year cladribine tablet course in 204 people with MS

Organisation: CladStop Study Group (University of Genoa and centres in Italy and Switzerland) · Italy

The CladStop study followed 204 people with relapsing multiple sclerosis (MS) at centres in Italy and Switzerland who had completed the approved two-year course of cladribine tablets. Follow-up started 24 months after the first dose and lasted 44.2 months on average. Over this time, 81 of 204 (39.7%) showed new disease activity (a relapse, new MRI activity or confirmed disability worsening); the estimated share still free of such activity was 82.8% after 12 months, 69.6% after 24 months, 63.3% after 36 months and 56.4% after 48 months. 42 people (20.6%) had a relapse (annualised relapse rate 0.06), 29.9% had new MRI activity and 7.4% had disability worsening confirmed after 6 months. 40.7% started another disease-modifying treatment, most often an anti-CD20 antibody or natalizumab. Adverse events after the course were recorded in 6 people, 2 of them serious (prostate cancer and enteritis).

Published by MyelinWatch: 5 Nov 2026

What this means for people with MS

For people who have finished cladribine tablets, these data describe what happened afterwards in routine care in two countries: disease activity stayed away for years in many people, but not in everyone, and when it returned it was mostly relapses or new MRI lesions rather than disability worsening. Follow-up continued after people started another treatment, so the figures for being free of disease activity also include time on those later treatments; the authors say they describe outcomes after completing cladribine, not the effect of cladribine alone. Among the 121 people who started no further treatment, 70.1% were estimated to be free of disease activity at 48 months, but this group was not chosen at random. The study has no comparison group, so it cannot show that cladribine caused the outcomes or compare it with other treatments; treatment decisions after the course were not random. Safety data came from routine records and stopped when another treatment began, and few people remained in the analysis at 48 months, so the later estimates are less precise. It does not justify a treatment change without review by a neurologist.

Read the update →Source: European Journal of Neurology — peer-reviewed research article ↗Source: PubMed — CladStop extended follow-up, PMID 42963188 ↗ Source: Europe PMC — open-access full text, PMC13722574 ↗

Research event/source date: 30 Oct 2026

Emerging treatmentsRegistered study in peopleStudy authorised in two EU countries; not a result

Phase 3 extension study authorised in two EU countries; recruitment not yet started

Frexalimab: long-term Phase 3 extension study authorised in Belgium and Austria

Organisation: Sanofi · France

The EU Clinical Trials Information System (CTIS) shows that Belgium authorised Sanofi's Phase 3 extension study LTS18002 (2026-525688-41-00) on 30 October 2026 and Austria on 1 November 2026. The study will look at the long-term safety and tolerability of frexalimab, an experimental antibody given into a vein or under the skin, in people with multiple sclerosis (MS). It is open only to people with relapsing MS or non-relapsing secondary progressive MS who complete earlier frexalimab studies on the study drug, including the Phase 3 studies FREXALT and FREVIVA. It plans 1,710 participants in total. Both countries are listed as authorised with recruitment pending; the estimated EU recruitment start is 15 February 2027.

Published by MyelinWatch: 2 Nov 2026

What this means for people with MS

Authorisation means the study may proceed; it does not mean that it has started, that anyone has received treatment in it, or that frexalimab works. No Phase 3 results are available yet. People who are not already in a frexalimab study cannot join this extension. Greece authorised the study later, on 2 November 2026 (see the separate update); frexalimab is not an available treatment in Greece.