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Emerging treatmentsResults from peopleExploratory findings in two people; no proven benefit

Phase 1, uncontrolled report of two treated participants; preprint

miv-cel CAR-T: immune findings in two people with progressive MS

Published by MyelinWatch:

Organisation
University of California, San Francisco research team
Study sponsor
Bruce Cree / University of California, San Francisco

What happened

A preprint posted on 11 September 2026 reports two women with treatment-refractory secondary progressive multiple sclerosis (MS) who received low-dose autologous anti-CD19 CAR-T cells, mivocabtagene autoleucel (miv-cel, also called KYV-101), after fludarabine and cyclophosphamide conditioning. CAR-T cells appeared in cerebrospinal fluid and exploratory immune measures changed. MRI findings were stable; observed disability scores changed, but with only two participants, no comparison group and conditioning treatment, these observations cannot establish that miv-cel caused benefit to patients. Reported adverse effects and laboratory abnormalities included grade 3 liver-enzyme elevation, neutropenia and lymphopenia in participant 1, with hypogammaglobulinaemia requiring immunoglobulin and a delayed rash; participant 2 had grade 4 lymphopenia and grade 1 cytokine-release syndrome treated with tocilizumab and dexamethasone. Conditioning chemotherapy may have contributed to blood-count changes.

What this means for people with MS

This is an experimental early human study, not evidence of an effective or available MS treatment or myelin repair. The preprint has not undergone journal peer review. The registry lists the Phase 1 study as active but not accepting new participants; the paper says further recruitment stopped after Kyverna, a study collaborator, shifted its development focus. The cited sources do not establish access in Greece.

About the approach studied in this programme: Miv-cel (KYV-101)

Miv-cel is made by collecting a person’s own T cells and engineering them to recognise CD19 on B cells. After preparatory chemotherapy, the cells are infused to deplete those B cells and potentially reset part of the immune response; whether this changes progressive MS outcomes remains unknown.

Approach source: Gupta et al. — September 2026 medRxiv preprint ↗

What kind of evidence exists?
Original medRxiv preprint, not peer reviewed; two people with secondary progressive MS
How reliable is this source?
Original medRxiv preprint for observations and recruitment explanation; ClinicalTrials.gov NCT06451159 for registered study design and listed status, checked separately

Related study or programme: Miv-cel (KYV-101) →

Source: Gupta et al. — medRxiv — original non-peer-reviewed medical preprint ↗Source: ClinicalTrials.gov — NCT06451159, Phase 1 study status and design ↗ Source: PubMed — preprint record PMID 42818477 ↗
Research event/source date
Published by MyelinWatch
Last substantive MyelinWatch update

Related substantive developments

Research event/source date:
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:

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:
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:

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.

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:
Emerging treatmentsResults from peopleSubgroup finding: significant in Hispanic or Latino participants, not significant in Black participants

Post hoc analysis of two completed Phase 3 trials in relapsing MS

OPERA trials: post hoc look at disability worsening in Black and Hispanic or Latino participants

Organisation: Keck School of Medicine, University of Southern California, with Genentech and Roche · United States

Researchers led by the University of Southern California, with authors from Genentech, Roche and other US centres, re-analysed the OPERA I and II trials, which compared ocrelizumab with interferon beta-1a for two years in relapsing multiple sclerosis (MS). In the interferon group, non-Hispanic Black and Hispanic or Latino participants had a higher risk of disability worsening confirmed after 24 weeks, measured with a combined (composite) disability measure, than non-Hispanic White participants (hazard ratio 3.0 and 2.3). Non-Hispanic Black and Hispanic or Latino participants also had more CD19-positive B cells at the start. In 1,138 participants who consented to genetic analysis, higher African or Americas genetic ancestry was also linked to higher risk. Ocrelizumab lowered B cells in all groups. Compared with interferon, it lowered the risk of this composite disability worsening in Hispanic or Latino participants (hazard ratio 0.38; 95% confidence interval 0.20–0.72). In the 65 Black participants the estimate also pointed to lower risk (hazard ratio 0.41), but the 95% confidence interval of 0.13–1.29 includes no difference, so the result is not statistically significant.

Published by MyelinWatch:

What this means for people with MS

This is not a new treatment or a new approval: ocrelizumab is already an approved MS treatment. The analysis was done after the trials ended, in small subgroups (only 65 Black participants), using self-reported race and ethnicity; it cannot show why risk differed and does not change treatment guidance. The authors conclude that ocrelizumab reduced risk regardless of race or ethnicity, but for Black participants the study alone does not establish this. It does not establish availability or reimbursement in Greece or support changing an individual treatment without a neurologist.

Read the update →Source: Multiple Sclerosis Journal (SAGE) — peer-reviewed primary article ↗Source: Multiple Sclerosis Journal — DOI 10.1177/13524585261496124 ↗ Source: ClinicalTrials.gov — OPERA I (NCT01247324), completed with posted results ↗ Source: ClinicalTrials.gov — OPERA II (NCT01412333), completed with posted results ↗