Emerging treatmentsResults from peopleMain goal missed; exploratory analyses only

Open-label extension and after-the-fact analyses of a Phase 2 study, reported by the sponsor

Vidofludimus calcium: new progressive MS analyses from a Phase 2 study that missed its main goal

Published by MyelinWatch: 5 Nov 2026

Organisation: Immunic · United States
Study sponsor: Immunic AG
Researcher: Robert J. Fox and colleagues

What happened

On 21 October 2026, Immunic reported new analyses of CALLIPER, a Phase 2 study that randomised 467 people with primary or secondary progressive multiple sclerosis (MS) to oral vidofludimus calcium or placebo. The study did not meet its main goal, percent brain volume change. In the open-label extension, which 387 people entered, the company says the favourable disability trends seen earlier were maintained among those who continued treatment, without giving figures in its announcement. Through the 27 January 2026 data cutoff, 6.5% had stopped; 44.4% had at least one treatment-emergent adverse event, 5.7% a serious one and 3.1% a liver-related one. An event during treatment does not show that the drug caused it. In an after-the-fact analysis with a newly proposed disability measure, people on the drug were 2.47 times more likely than those on placebo to have 24-week confirmed disability improvement, and 1.5 times more likely to have a better outcome with a second method. Other posters covered an exploratory link between Epstein-Barr virus T-cell signatures and a thinking-speed test, and laboratory and mouse findings.

What this means for people with MS

Because CALLIPER missed its main goal, these analyses cannot show that the drug helps people with progressive MS. The extension has no placebo group, the disability analyses were done after the fact, and the proposed measure is not an established study endpoint. Immunic reports a nominal p=0.037 for the 2.47 result; this is not adjusted for multiple comparisons and is not confirmatory evidence. Laboratory and mouse results may not apply to people. Vidofludimus calcium is not approved anywhere. Immunic expects top-line results of the Phase 3 ENSURE trials in relapsing MS by the end of 2026 and plans a Phase 3 trial in progressive MS.

What kind of evidence exists?: Immunic announcement of four conference posters; not peer reviewed
How reliable is this source?: Immunic's own announcement of conference posters, not peer-reviewed; the posters were not read. The ClinicalTrials.gov record for CALLIPER was last updated in April 2024 and shows an unknown status, so it does not confirm the current state of the extension.

Source: Immunic — official company announcement ↗Source: ClinicalTrials.gov — CALLIPER, NCT05054140 ↗ Source: ClinicalTrials.gov — ENSURE-1, NCT05134441 ↗ Source: ClinicalTrials.gov — ENSURE-2, NCT05201638 ↗

Research event/source date: 21 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.