Long-Term Extension Data Demonstrates Sustained Effect of Vidofludimus Calcium in Relapsing-Remitting Multiple Sclerosis

Andreas Muehler, MD, MBA, chief medical officer at Immunic

Newly announced data from the open-label extension (OLE) period of the phase 2 EMPhASIS trial (NCT03846219) showed that patients with relapsing-remitting multiple sclerosis (RRMS) treated with vidofludimus calcium (Immunic) maintained low rates of disability progression over a 144-week period. The findings, which also showed no new safety signals over a 5.5-year period, further support vidofludimus calcium as a potential treatment for RRMS.¹

Of the 268 patients that started the double-blind main treatment period, 254 continued into the OLE, where they received 30 mg of vidofludimus calcium once-daily. At the time of data cutoff (January 14, 2025), 182 patients (71.6%) were evaluated up to week 144, translating to approximately 952 overall treatment years.

At week 144, 92.3% of treated patients remained free of 12-week confirmed disability worsening (CDW), and 92.7% were free of 24-week CDW. Of the 29 CDW events confirmed between week 12 and week 144 after the trigger event, 44.8% were linked to relapse-associated worsening (RAW) and 13.8% to progression independent of relapse activity (PIRA). In terms of safety, treatment with the investigational agent led to low discontinuation rates, treatment-emergent and serious adverse events, as well as no new safety signals observed throughout the extension period.

"It is meaningful to see that patients treated with vidofludimus calcium during the OLE period of our phase 2 EMPhASIS trial in RRMS experienced a low rate of confirmed disability worsening (CDW) events, as measured by the Expanded Disability Status Scale (EDSS)," Andreas Muehler, MD, MBA, chief medical officer at Immunic, said in a statement.¹ "This data, representing approximately 952 treatment years, further underlines our belief that vidofludimus calcium holds great potential to effectively manage the disease, help preserve neurological function, allow patients to maintain independence and improve long-term quality of life."

Vidofludimus calcium, also being tested in progressive forms of MS, is a selective dihydroorotate dehydrogenase (DHODH) inhibitor. It works by inhibiting de novo pyrimidine synthesis, selectively reducing proliferation of activated T and B lymphocytes without impairing resting immune cells. This selective immune modulation contrasts with previously approved agents for RRMS, including S1P modulators, anti-CD20 antibodies, interferons, and teriflunomide, which is also a DHODH inhibitor but with a different chemical structure and broader off-target effects.

Daniel Vitt, PhD

"This new data from the OLE period is very encouraging and continues to corroborate the prior strong results we observed in our phase 2 EMPhASIS trial in RRMS," Daniel Vitt, PhD, chief executive officer at Immunic, said in a statement.¹ "The ability to maintain remarkably low rates of disability progression is among the most important unmet needs in relapsing MS despite the availability of multiple anti-inflammatory drugs approved for the treatment of MS relapses. By delaying disease progression, MS patients maintain greater independence, face a lower burden in managing their symptoms and experience more favorable long-term outcomes."

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Vitt went on to note that these data, along with recent topline data from the phase 2 CALLIPER trial (NCT05054140) in progressive MS, further demonstrates the agent’s ability to slow disease progression in MS. CALLIPER, a double-blind, placebo-controlled exploratory study, featured patients with primary progressive MS (n = 152) and non-active secondary progressive MS (n = 268) testing 45 mg daily doses of vidofludimus calcium or placebo for up to 120 weeks.²

Data from the study announced in April showed a 20% relative risk reduction of 24-week CDW events in the overall population, with an even greater effect observed within the primary-progressive group (30% reduction). Less pronounced, but still notable, effects were seen in the non-active group, with a 15% reduction relative to those on placebo. Treatment with the investigational agent led to a 29% reduced relative risk in 24-week CDW events compared with placebo, which was observed across various subpopulations, regardless of inflammatory gadolinium-enhancing lesion activity at baseline or during the study.

Vidofludimus calcium, previously known as IMU-838, had data from EMPhASIS previously published in Neurology, Neuroimmunology & Neuroinflammation in mid-2024. In the 268-patient cohort, the mean cumulative combined unique active (CUA) lesions was 5.8 (95% CI, 4.1-8.2) for placebo (n = 81), 5.9 (95% CI, 3.9-9.0) for 10-mg treatment group (n = 47), 1.4 (95% CI, 0.9-2.1) for 30-mg treatment group (n = 71), and 1.7 (95% CI, 1.1-2.5) for 45-mg treatment group (n = 69) over 24 weeks. Notably, there was a dose-dependent decrease in serum neurofilament light for treated patients.³

In terms of safety, treatment-emergent adverse events were reported in 43% of patients receiving placebo, compared with 23% in the 10-mg IMU-838 group and 37% across all IMU-838 dose groups. The incidence of liver enzyme elevations and infections was comparable between the placebo and IMU-838 groups, and no new safety signals were identified with the treatment.

REFERENCES
1. Immunic Reports New, Positive Long-Term Open-Label Extension Data From Phase 2 EMPhASIS Trial of Vidofludimus Calcium in Relapsing-Remitting Multiple Sclerosis. News release. Immunic. June 24, 2025. Accessed June 24, 2025. https://www.prnewswire.com/news-releases/immunic-reports-new-positive-long-term-open-label-extension-data-from-phase-2-emphasis-trial-of-vidofludimus-calcium-in-relapsing-remitting-multiple-sclerosis-302489105.html
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 June 24, 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. Fox RJ, Wiendl H, Wolf C, et al. Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis: Extended Results of a Placebo-Controlled Phase 2 Trial. Neurol Neuroimmunol Neuroinflamm. 2024;11(3):e200208. doi:10.1212/NXI.0000000000200208