Emerging treatmentsResults from peopleMRI markers improved; clinical meaning and safety need assessment

MRI analysis from Phase 3 trials, presented at a conference by the sponsor

Fenebrutinib: Roche reports smaller chronic MRI lesions in Phase 3 trials

Published by MyelinWatch: 5 Nov 2026

Organisation: Roche
Study sponsor: F. Hoffmann-La Roche Ltd
Researcher: Jiwon Oh and colleagues

What happened

Roche reported a late-breaking MRI analysis of its Phase 3 fenebrutinib trials at MSToronto2026, presented on 23 October 2026. It looked at slowly expanding lesions and paramagnetic rim lesions, MRI signs linked to chronic inflammation in the brain. Roche reported that the volume of slowly expanding lesions was up to 30% lower than with the comparison drug, in relapsing multiple sclerosis (MS) over 96 weeks and in primary progressive MS over 120 weeks. It also reported 62% less accumulation of paramagnetic rim lesions in relapsing MS. MS Australia's meeting summary gives lesion-volume reductions of 30.5% against teriflunomide in relapsing MS and 27.5% against ocrelizumab in primary progressive MS, and says the difference in new rim lesions was statistically significant in relapsing MS but not in primary progressive MS. In a separate pooled analysis of the relapsing MS trials, Roche reported a 55% lower annualised relapse rate than teriflunomide over 96 weeks, 23% less yearly brain volume loss, and a 16% reduction in 12-week composite confirmed disability progression.

What this means for people with MS

These are MRI measures, and a change in them does not by itself show that fenebrutinib prevents disability. The statement that the drug directly targets chronic inflammation is Roche's interpretation. Roche's announcement of these findings gives no safety data, so the earlier reports of more liver-enzyme elevations in FENtrepid and an imbalance in deaths across the trials remain relevant. Fenebrutinib is not approved; Roche said on 30 September 2026 that the FDA had accepted its application for review.

About the approach studied in this programme: Fenebrutinib

Fenebrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK), a protein involved in B-cell and other immune-cell signalling. Researchers test whether altering this signalling can limit MS activity and disability progression; the mechanism does not itself establish clinical benefit or myelin repair.

Approach source: Roche — fenebrutinib development announcement ↗

What kind of evidence exists?: Roche announcement of a late-breaking conference analysis; not peer reviewed
How reliable is this source?: Roche's own announcement of conference results, not peer-reviewed. The conference abstract could not be read. The figures attributed to MS Australia come from its patient-organisation meeting summary, not from a primary source.

Understand the BTK treatment family →

Source: Roche — official company announcement ↗Source: MS Australia — research updates from MSToronto2026 ↗ Source: Roche — FDA application and earlier safety findings, 30 September 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.