CALLIPER Extension Data Show Sustained Disability Outcomes With Vidofludimus Calcium in Progressive MS

New open-label extension (OLE) data from the phase 2 CALLIPER trial (NCT05054140), presented at the 10th Joint ACTRIMS-ECTRIMS Meeting (MSToronto2026), held October 21–23, in Toronto, Canada, showed that favorable disability trends observed with vidofludimus calcium (Immunic) during the double-blind period were maintained among patients with progressive multiple sclerosis (MS) who continued treatment. The safety and tolerability profile in the extension appeared consistent with that of the double-blind period.¹

The analysis was presented by lead author Robert J. Fox, MD, staff neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic, and coordinating investigator of CALLIPER. Only 6.5% of patients discontinued the OLE through the January 27, 2026, data cutoff.

"The data presented at MSToronto2026 provide complementary clinical and mechanistic evidence supporting the differentiated profile of vidofludimus calcium across the multiple sclerosis (MS) spectrum,” Erik Lundgren, chief executive officer of Immunic, said in a statement.⁴ "Importantly, the new CALLIPER open-label extension (OLE) analyses provide favorable long-term follow-up of the disability signals observed during the double-blind treatment period.”

Trial Design and Safety

CALLIPER randomly assigned 467 patients with primary or secondary progressive MS 1:1 to vidofludimus calcium 45 mg once daily or placebo. The double-blind portion did not meet its primary end point of percent brain volume change, although exploratory imaging and clinical outcomes showed directionally favorable signals. During that period, rates of treatment-emergent adverse events (TEAEs) were 69.4% with vidofludimus calcium vs 68.5% with placebo, and rates of serious adverse events were 8.1% vs 6.5%, respectively, with no new safety signals or Hy's law–range cases.

Of 387 participants who entered the OLE, 44.4% had at least 1 TEAE and 5.7% had a serious TEAE. Liver-related TEAEs occurred in 3.1%, and 1.8% discontinued because of a TEAE. Quantitative OLE disability effect sizes were not reported in the company's announcement.

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Additional CALLIPER Analyses

In an exploratory analysis presented by Amelie Schreieck, PhD, senior manager of biomarker development at Immunic, vidofludimus calcium significantly reduced Epstein-Barr virus (EBV)–specific T-cell receptor β chain (TRB) sequence matches vs placebo (−0.65 matches; P = .0004), whereas influenza A–specific matches were unchanged (+0.08; P = .5983). In a post hoc analysis, reductions in EBV-specific TRB matches were associated with improved Symbol Digit Modalities Test scores.²

A separate post hoc analysis, presented by James Myles, global head of biostatistics at Immunic, applied 2 methods designed to capture disability improvement and worsening together. By Confirmed Disability Change, treated patients were 2.47 times more likely to achieve 24-week confirmed disability improvement (nominal P = .037). By Generalized Pairwise Comparisons on Expanded Disability Status Scale outcomes, they were 1.5 times more likely than placebo recipients to have a better outcome (P = .042).³ Neither method is an established regulatory end point.

Clinical Context and Next Steps

Vidofludimus calcium is an investigational oral small molecule that activates nuclear receptor-related 1 (Nurr1) and selectively inhibits dihydroorotate dehydrogenase (DHODH), a combination intended to address both neurodegeneration and inflammation. More than 3500 individuals have been exposed to the agent to date.⁴

The OLE lacks a placebo comparator, and patients who continued treatment may differ from those who did not. The EBV and bidirectional end point findings are exploratory or post hoc, with nominal P values unadjusted for multiplicity. Immunic plans to initiate a phase 3 trial in progressive MS later in 2026, and topline results from the fully enrolled phase 3 ENSURE trials in relapsing MS are expected by year-end.⁴

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REFERENCES
1. Fox RJ, et al. Evaluation of disability outcomes from the open-label extension of CALLIPER: a phase 2 trial of vidofludimus calcium in progressive multiple sclerosis. Presented at: MSToronto2026; October 21-23; Toronto, Canada. Poster P0387.
2. Schreieck A, et al. Anti-EBV T-cell receptor repertoire reduction is linked to enhanced cognitive performance in progressive multiple sclerosis: evidence from the phase 2 CALLIPER trial with vidofludimus calcium, a direct Nurr1 activator and selective DHODH inhibitor. Presented at: MSToronto2026; October 21-23; Toronto, Canada. ePoster EP2473.
3. Myles J, et al. Bidirectional disability changes in progressive multiple sclerosis patients: a proposed endpoint to capture full treatment effects. Presented at: MSToronto2026; October 21-23; Toronto, Canada. ePoster EP2205.
4. Immunic presents new clinical, biomarker, and preclinical data for vidofludimus calcium in four poster presentations at MSToronto2026 – the 10th Joint ACTRIMS-ECTRIMS Meeting. News release. Immunic, Inc. October 21, 2026. Accessed October 21, 2026. https://ir.imux.com/2026-10-21-Immunic-Presents-New-Clinical,-Biomarker,-and-Preclinical-Data-for-Vidofludimus-Calcium-in-Four-Poster-Presentations-at-MSToronto2026-the-10th-Joint-ACTRIMS-ECTRIMS-Meeting