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IMU-838 daily doses of 30-mg and 45-mg suppressed the development of gadolinium-enhancing lesions by 78% and 74% compared with the placebo at 24 weeks in relapsing-remitting multiple sclerosis.
Daniel Vitt, PhD
(Credit: Immunic)
New data from the phase 2 EMPhASIS trial (NCT03846219) published in Neurology Neuroimmunology & Neuroinflammation showed that vidofludimus calcium formulation (IMU-838) given at daily doses of 30-mg and 45-mg but not of 10-mg decreased the cumulative number of active lesions compared with placebo among patients with active relapsing-remitting multiple sclerosis (RRMS) and at least 1 gadolinium-enhancing (Gd+) brain lesion in the last 6 months, establishing the lowest efficacious dose.1,2
Among 268 patients, 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. Researchers reported a decrease in serum neurofilament light chain decreased in a dose-dependent manner. Notably, only 3 patients in the placebo group (3.7%) and 3 patients in any dose group of IMU-838 (1.6%) had confirmed disability worsening after 24 weeks.
"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," Daniel Vitt, PhD, chief executive officer and president at Immunic, said in a statement.2 "As reported, a dose-dependent effect of vidofludimus calcium on the suppression of new CUA MRI as well as Gd+ lesions was demonstrated along with an encouraging initial signal towards reducing 12-week and 24-week confirmed disability worsening events as compared to placebo during the double-blind treatment period.”
In this phase 2, randomized, placebo-controlled trial, patients with RRMS, participants were aged between 18 and 55 years, and experienced at least 2 relapses in the last 2 years or at least 1 relapse in the last year, and had at least 1 gadolinium-enhancing brain lesion in the past 6 months. Investigators randomly assigned patients 1:1:1 to IMU-838 30-mg or 45-mg, or placebo in cohort 1 and IMU-838 10-mg or placebo 4:1 in cohort 2 for 24 weeks. The primary end point was the cumulative number of CUA lesions at 24 weeks after treatment and the secondary end points were clinical outcomes as well as safety.
READ MORE: Stable MRI in Multiple Sclerosis Reveals Relapses as Acute Clinical Events
In terms of safety, investigators observed that treatment-emergent adverse events were reported in 35 patients in the placebo group (43%) compared with 11 patients and 71 patients in the 10-mg (23%) or any dose of IMU-838 groups (37%), respectively. Additional safety findings showed that incidence of liver enzyme elevations and infections were similar between placebo and any dose of IMU-838. Furthermore, researchers did not observe any new safety signals with the treatment.
“The findings impressively underline the drug's combined neuroprotective and anti-inflammatory effects. Meanwhile, we continue to enroll patients in our twin phase 3 ENSURE trials in relapsing multiple sclerosis (MS), from which we expect to report an interim futility analysis in late 2024, with the top-line readout of the first of the ENSURE trials anticipated in the second quarter of 2026,” Vitt said in a statement.2
IMU-838, a known inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells, has shown promising results in previous studies for treating patients with relapsing forms of MS. The agent has demonstrated a mechanistic ability to selectively act on hyperactive T and B cells while leaving other immune cells largely unaffected and thus enabling normal immune system function to occur.
In an interim analysis of the phase 2 CALLIPER (NCT05054140) assessing the efficacy and safety of IMU-838 in patients with progressive MS, results showed reductions in neurofilament light chain (Nfl) after 24 weeks of treatment. Notably, these reductions were consistent across progressive MS subtypes.3 In the study, investigators randomized 467 patients with primary progressive MS (35.2%), non-active secondary primary MS (59.5%) and active secondary primary MS (7.9%) 1:1 to IMU-838 or placebo for up to 120 weeks.
These findings were presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, by lead author Robert J. Fox, MD, staff neurologist at the Mellen Center for Multiple Sclerosis at Cleveland Clinic. Fox recently sat down with NeurologyLive® at the meeting to discuss how IMU-838 differs from another DHODH inhibitors. He also talked about the key pathways targeted by IMU-838 in addressing inflammation and progression in MS, as well as how the observed reduction in neurofilament levels correlates with improved outcomes in the disease.
