Early treatment may ease long-term disability in progressive MS

Early treatment with the experimental oral therapy vidofludimus calcium (IMU-838) may lead to less long-term disability in people with progressive forms of multiple sclerosis (MS), according to new data from the CALLIPER Phase 2 trial and its extension.

Immunic, the company developing vidofludimus calcium, presented the findings at MSToronto2026, the 10th joint meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis, held last week in Toronto.

“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, CEO of Immunic, said in a company press release. “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.”

Vidofludimus calcium is thought to have both anti-inflammatory and nerve-protecting properties. This is expected to address the acute inflammatory attacks that drive MS relapses (periods of new or worsening symptoms) in people with relapsing forms of the disease, as well as the chronic inflammation and nerve cell death that drive gradual disability accumulation across MS types.

Immunic is testing vidofludimus calcium as a potential treatment for both relapsing and progressive forms of MS. The new analyses presented at MSToronto2026 come from CALLIPER (NCT05054140), which enrolled 467 adults with either secondary progressive MS or primary progressive MS.

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Improvements across patient groups

In the main CALLIPER study, participants were randomly assigned to receive vidofludimus calcium or a placebo for about 2.5 years. The study missed its main goal, which was to show that vidofludimus calcium reduced brain atrophy (shrinkage). Nonetheless, analyses showed that patients given vidofludimus calcium were less likely to experience confirmed disability worsening and more likely to experience confirmed disability improvement.

This was observed across key patient subgroups, including patients with PPMS, those with nonactive SPMS, and individuals without active lesions at baseline.

After the placebo-controlled part of CALLIPER ended, 387 participants entered the open-label extension, in which all are being treated with vidofludimus calcium and monitored for up to eight years for long-term outcomes.

Immunic presented data covering more than four years of follow-up in the extension in a poster titled, “Evaluation of Disability Outcomes from the Open-Label Extension of CALLIPER: A Phase 2 Trial of Vidofludimus Calcium In Progressive Multiple Sclerosis.”

Results showed that patients who were given vidofludimus calcium in the main study had consistently better long-term disability outcomes, including lower rates of confirmed disability worsening and higher rates of confirmed disability improvement, than those who received a placebo in the main study and started vidofludimus only in the extension.

Again, the benefits seemed consistent across people with PPMS, nonactive SPMS, and those with no signs of inflammatory disease activity. However, most of these were trends that did not reach statistical significance, so the results should be interpreted with caution.

The researchers concluded that vidofludimus calcium treatment “showed favorable disability trends, including improvement, that were sustained up to 4.3 years of follow-up.”

The causes of MS aren’t well understood, but infection with Epstein-Barr virus (EBV) is a well-established risk factor. While the link between EBV and MS is also not fully understood, some scientists believe that immune cells trying to attack the virus may inadvertently trigger MS-driving inflammation.

A separate exploratory analysis from the CALLIPER study showed that vidofludimus calcium reduced the number of T-cells (a type of immune cell) with receptors capable of recognizing EBV. The analysis also showed that patients with a greater reduction in EBV-specific T-cells were more likely to experience improvement in a standard cognitive test.

That analysis was also presented at MSToronto, in a poster titled, “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.”

“Reduced EBV-specific [T-cells] corresponded to improved [cognitive] scores, suggesting an association between EBV-related immune activity and cognition in [progressive forms of MS],” the researchers wrote.

Immunic is planning a Phase 3 trial program to further test vidofludimus calcium in people with progressive forms of MS. The company is also running two Phase 3 trials, ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638), testing vidofludimus calcium in people with relapsing forms of the disease. Results from those studies are expected in the coming months.

Lundgren said the analyses presented at MSToronto “further support the clinical and scientific rationale for our planned Phase 3 program in progressive MS, which we expect to initiate later this year, while we also approach the top-line results from our fully enrolled Phase 3 ENSURE trials in relapsing MS, expected by year-end 2026.”