CALLIPER Subpopulation Data Support Therapeutic Effect of Vidofludimus Calcium in Primary Progressive MS

Newly presented subpopulation data from a phase 2 study (NCT05054140) showed that treatment with investigational vidofludimus calcium (VidoCa; Immunic) may have a modest clinical effect in slowing disability progression in patients with primary progressive multiple sclerosis (PPMS), including those without active inflammation at baseline. Overall, the consistent hazard ratios below 1.0 for time to confirmed disability worsening (CDW) across multiple PPMS subgroups warrant a larger, phase 3 trial to confirm the drug’s effects.¹

Among a cohort of 467 participants, the double-blind, placebo-controlled trial enrolled 152 patients with PPMS, aged 18 to 65 years, with baseline Expanded Disability Status Scale (EDSS) score of 3.0 to 6.5. For those with PPMS, the difference of least square mean (ΔLSM, all re-baselined at 6 months) of the annualized rate for percent brain volume change (PBVC), the study’s primary end point, was 0.04 (VidoCa: LSM, –0.78; placebo; –0.82; P >.03). In addition the difference of LSM was 0.05 between the cohorts for thalamus volume (VidoCa: –0.55; placebo: –0.61; P >.03).

These findings were presented as late-breaking data at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, 2026, in Barcelona, Spain. Led by Robert J. Fox, MD, staff neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic, patients were randomly assigned to either 45 mg VidoCa or matching placebo, with the majority of participants (40.8%) under aged 45 years at the time of administration.

Coming into the study, baseline EDSS was 5.5 or less for 61.3% of patients with PPMS, and at least 6 for 38.7% of the cohort. In addition to PBVC, the study’s other main end point was 24-week CDW as assessed on a composite of EDSS, 9-Hole Peg Test, and Timed 25-Foot (24wCDW-COMP). Within the PPMS subpopulation, the time to 24wCDW-COMP reached a hazard ratio of 0.0770 (n = 152; 95% CI, 0.401-1.479; P >.03) for the overall PPMS subpopulation.

At baseline, 15.6% of patients with PPMS on VidoCa had gadolinium-enhancing (Gd+) MRI lesions (20.0% for placebo). Within this group, results revealed a 24wCDW-COMP hazard ratio of 0.687 (n = 125; 95% CI, 0.336-1.404; P >.03). In addition, this group demonstrated hazard ratios of 0.662 (n = 125; 95% CI, 0.293-1.460; P = .030) for time to 24-week CDW based on EDSS (24wCDW-EDSS). For comparison, in the overall PPMS population, hazard ratios for time to 24wCDW-EDSS were 0.675 (n = 152; 95% CI, 0.324-1.406; P = .29).

"The observed treatment effect was maintained in the subgroup of PPMS patients without Gd+ at baseline which supports clinically measurable neuroprotective effects of vidofludimus calcium, presumably due to the Nurr1 activation mechanism," the study authors wrote.

READ MORE: Ocrelizumab Demonstrates Efficacy Over Placebo in Phase 3b ORATORIO-HAND Trial of Primary Progressive MS

Vidofludimus calcium, a nuclear receptor related 1 (Nurr1) activator, is an oral, once-daily investigational agent that inhibits dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme in de novo pyrimidine synthesis. The medication uniquely activates Nurr1, a nuclear receptor that regulates both inflammation and neuronal survival in the central nervous system; by doing so, it is thought to suppress NF-κB–driven neuroinflammation, a major contributor to chronic MS progression.

CALLIPER included both patients with PPMS and non-active secondary progressive MS (naSPMS; n = 268) who were followed for a 120-week double-blind period. Data released earlier this year revealed an overall 20% relative risk reduction of 24-week CDW events in the overall population, with less benefits observed (15% reduction) in the naSPMS group relative to placebo.²

Among MRI end points, the most pronounced effect was observed in thalamic brain volume, where vidofludimus calcium treatment led to a 20% lower annualized atrophy rate compared with placebo. For overall brain volume loss, the annualized rate of percent brain volume change showed a more modest 5% relative improvement with active treatment. Additionally, vidofludimus calcium significantly reduced new or enlarging T2 lesions over time, with a mean percent change of –0.22% at month 24 versus +2.97% for placebo, representing a 3.19% treatment benefit.

Vidofludimus calcium is currently being examined in 2 phase 3 trials of relapsing MS, expected to be completed in 2026. The studies, dubbed ENSURE-1 and ENSURE-2, are 2 identical, randomized, double-blind trials testing the efficacy and safety of 30 mg daily doses of vidofludimus calcium in a cohort of 1050 adults with relapsing MS.³

Click here for more ECTRIMS 2025 coverage.

REFERENCES
1. Efficacy and Safety of Vidofludimus Calcium, a novel Nurr1 activator and DHODH inhibitor, in Primary Progressive Multiple Sclerosis (PPMS): Subpopulation Data from the Phase 2 CALLIPER Trial. Presented at: 2025 ECTRIMS Congress; September 24-26; Barcelona, Spain. ABSTRACT P417
2. Immunic Announces Vidofludimus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial. News release. Immunic. April 30, 2025. Accessed September 22, 2025. https://imux.com/immunic-announces-vidofludimus-calcium-reduced-risk-of-disability-worsening-by-30-in-primary-progressive-multiple-sclerosis-patients-from-phase-2-calliper-trial/
3. Immunic Announces Positive Outcome of Interim Analysis of Phase 3 ENSURE Program of Vidofludimus Calcium in Relapsing Multiple Sclerosis. News release. Immunic. October 22, 2024. Accessed September 22, 2025. https://finance.yahoo.com/news/immunic-announces-positive-outcome-interim-103000104.html