Immunic (NASDAQ:IMUX), Inc. (Nasdaq: IMUX) 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
The paper, lead authored by coordinating investigator,
"The publication of our phase 2 EMPhASIS trial results for both study cohorts with an extended dose range in such a prestigious peer-reviewed journal represents further evidence of the strength of these findings for vidofludimus calcium in patients with RRMS," stated
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 highest 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.
Increases in disability over a pre-defined disability change threshold (defined as trigger events and measured by Expanded Disability Status Scale, EDSS) during the double-blind treatment period were confirmed after 12 or 24 weeks, designating them confirmed disability worsening (CDW) events. The number of patients who had confirmed 12- or 24-weeks CDW events was 3.7% for patients receiving placebo and only 1.6% for patients receiving any dose of vidofludimus calcium.
Finally, the pooled data set also reinforced that vidofludimus calcium was well-tolerated, in general, and that its safety profile was similar to the placebo group. Across cohorts 1 and 2, a total of 268 patients were randomized to 10 mg (n=47), 30 mg (n=71), or 45 mg (n=69) of vidofludimus calcium or placebo (n=81).