Immunic, Inc. announced that data from its phase 2 EMPhASIS trial of lead asset, vidofludimus calcium (IMU-838), in patients with relapsing-remitting multiple sclerosis (RRMS) has been published online on April 25, 2024 in Neurology® Neuroimmunology & Neuroinflammation, an official journal of the American Academy of Neurology. The paper, lead authored by coordinating investigator, Robert J. Fox, M.D., Staff Neurologist, Mellen Center for Multiple Sclerosis, Vice-Chair for Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, is entitled, "Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis: Extended Results of a Placebo-Controlled Phase 2 Trial." Dr. Fox receives consulting fees for serving as an advisor to Immunic. Vidofludimus calcium, an orally available first-in-class nuclear receptor related 1 (Nurr1) activator and next-generation dihydroorotate dehydrogenase (DHODH) inhibitor, was shown to have suppressed MRI disease activity compared to placebo in patients with RRMS in the first cohort of the multicenter, double-blind, randomized, placebo-controlled phase 2 EMPhASIS trial, achieving all primary and key secondary endpoints with high statistical significance. The results of study cohort 1, exploring the doses of 30 mg and 45 mg of vidofludimus calcium in RRMS patients versus placebo, were published in Annals of Clinical and Translational Neurology in 2022 (Fox RJ, et al.

Ann Clin Transl Neurol. 2022;9(7):977-987). Given that both doses of 30 mg and 45 mg of vidofludimus calcium showed comparable robust activity on multiple endpoints, the trial enrolled an additional cohort of patients to receive a lower dose of vidofludimus calcium in order to further investigate a dose-response relationship by extending the trial to a broader dose range.

Study cohort 2 explored the dose of 10 mg of vidofludimus calcium versus placebo. Extended results from the pooled EMPhASIS data (cohorts 1 and 2, including comparison to the pooled placebo group from both study cohorts) were summarized in more detail in this latest peer-reviewed article. The pooled data showed that, compared to placebo, vidofludimus calcium suppressed the development of new CUA MRI lesions with daily doses of 30 mg and 45 mg up to week 24 by 76% and 71%, respectively. In addition, compared to placebo, vidofludimus calcium suppressed the development of Gd+ lesions with daily doses of 30 mg and 45 mg up to week 24 by 78% and 74%, respectively.

Such robust anti-inflammatory effects were not seen with 10 mg, establishing 30 mg as the lowest effective dose. Serum neurofilament light chain (NfL), which is thought to correlate with neuronal destruction, decreased in a dose-dependent manner up to the higher tested dose of vidofludimus calcium by 9% (10 mg), 18% (30 mg) and 26% (45mg) compared to placebo, respectively, suggesting that the effect on NfL has a different dose-response pattern which contrasts with that observed with new CUA or Gd+ by MRI lesions.