New research has yielded promising results for a potential new therapeutic agent -- vidofludimus calcium (IMU-838; Immunic Therapeutics) -- in relapsing-remitting multiple sclerosis (RMSS).
The phase-2 clinical trial concluded that the novel agent -- a next-generation, small molecule DHODH inhibitor -- is as effective as other first-line and oral medications in relapsing-remitting MS, with a favorable safety profile.
In a presentation to the 8th Joint ACTRIMS-ECTRIMS meeting (abstract 1409), an international, multi-center team of researchers explained that IMU-838 is intended to be a selective, once-daily medication for relapsing-remitting MS. “It is in the same class as teriflunomide, but lacks off-target effects on kinase -- which may reduce side effects -- and also has a much shorter half-life,” said lead author Robert J. Fox, MD, a Staff Neurologist at the Mellen Center for Multiple Sclerosis, Cleveland Clinic Foundation, Cleveland, Ohio.
To test the safety and efficacy of the agent, Dr. Fox and his colleagues enrolled 209 adult MS patients (aged 18-55 years) into the so-called EMPhASIS trial. All of the patients had relapsing-remitting MS with evidence of disease activity in the previous 12-24 months.
Patients received either 45 mg IMU-838 (n=69), 30 mg IMU-838 (n=71), or placebo (n=69) over a period of 24 weeks. The study’s primary endpoint was the efficacy of IMU-838 relative to placebo based on the cumulative number of new combined unique active lesions. In total, 198 patients completed the 24-week trial period: 64 in the placebo group, 69 in the 30 mg IMU-838 group, and 65 in the 45 mg IMU-838 group.
Fox noted the study met its primary and key secondary endpoints. Indeed, patients who received the 45 mg IMU-838 dose demonstrated a 62% reduction in combined active lesions compared with their counterparts who received placebo (p=0.002). Furthermore, those who received the 30 mg dose of the study drug had a 70% reduction in such lesions (p<0.0001). These beneficial effects, the researchers added, were observed across many patient subgroups as well.
Analysis of several other endpoints also demonstrated consistent benefit with IMU-838 administration. The time course of Gd-enhancing MRI lesion reduction was consistent throughout follow-up. Specifically, 59.2% of patients receiving the 30 mg dose had no gadolinium MRI lesions over 24-week treatment period, compared with 49.3% of those who received the 45 mg dose and 37.7% of those taking placebo.
Although the investigators did not plan formal statistical analyses for secondary endpoints, these also demonstrated marked advantages for IMU-838 compared with placebo, including the median percentage change in serum neurofilament, annualized relapse rate, and change in Expanded Disability Status Scale. Finally, patient satisfaction questionnaires showed that individuals receiving the study drug had a perception of increased effectiveness compared with placebo and were very satisfied with IMU-838 treatment.
With respect to safety, there was no difference in the rate of adverse events or serious adverse events between treatment groups. Indeed, 45.1% of patients in the 30 mg IMU-838 group experienced treatment-emergent adverse events, compared with 40.6% of those receiving 45 mg of the study drug and 43.5% of those taking placebo.
Three patients had serious treatment-emergent adverse events, one in the placebo group and two in the 30 mg IMU-838 group. No deaths occurred during the trial. Analyses of renal and hepatic toxicity found no increase in liver or renal events compared with placebo. Similarly, no signal was observed for any hepatotoxicity or elevations of liver enzymes. Finally, treatment discontinuations due to adverse events were comparable between the placebo and treatment groups.
The investigators concluded that the trial met both its primary and key secondary outcomes, with a 62-70% decrease in MRI lesions across the two treatment groups.
“Overall,” Dr. Fox said, “these results compare quite favorably with other first-line and oral therapies in relapsing MS.”
A phase-3 trial program is currently being planned.
