Oral RRMS Therapy Safely Lowers Active Lesions in Phase 2 Trial, Data Show

Immunic Therapeutics‘s IMU-838, a selective immune system modulator, can safely lower the number of brain lesions in people with relapsing-remitting multiple sclerosis (RRMS), top-line Phase 2 clinical trial data suggest.

Findings show the trial met its primary goal with statistical significance — a reduction in active lesions (gadolinium positive) on imaging scans, the company reported. It is also reported to have met key secondary goals.

“We believe this data strongly supports our goal of developing IMU-838 as an easy, safe and convenient oral treatment option for patients with RRMS and other autoimmune diseases,” Andreas Muehler, MD, chief medical officer of Immunic, said in a press release.

“We are extremely encouraged by these results and intend to now focus on the development plan with the goal of eventually making IMU-838 available as a best-in-class, once-daily oral therapy for RRMS,” Muehler added.

IMU-838 (vidofludimus calcium) is a small molecule that works by blocking the activity of an enzyme called dihydroorotate dehydrogenase (DHODH). This is believed to reduce the activity of B-cells and T-cells, immune cells that drive inflammation that can damage the nervous system in multiple sclerosis.

The Phase 2 clinical trial EMPhASIS (NCT03846219) evaluated the efficacy and safety of IMU-838 in 209 adults with RRMS across Eastern Europe. All were randomized to one of two doses of IMU-838 — 30 mg or 45 mg — or to a placebo given once daily for 24 weeks.

Of these patients, 69 were given IMU-838 at 45 mg/day, 71 were randomized to IMU-838 at 30 mg/day, and 69 to a placebo. Most enrolled, 197 people, completed the 24-week study and now have the option of continuing or starting treatment in its open-label and long-term extension phase.

The trial’s primary endpoint — its main measurement of efficacy — was the number of active brain lesions visible on an MRI scan. An MRI was performed at the study’s start (a baseline measure) and at six, 12, 18, and 24 weeks later.

Compared with placebo, treatment with IMU-838 at 45 mg/day reduced the number of active lesions by 62% up to week 24, while treatment with 30 mg/day IMU-838 reduced these lesions by 70%. Both differences were statistically significant.

Marked benefits with IMU-838’s use, relative to placebo, were also across secondary endpoints, including other MRI measures, relapse-related events, and other clinical endpoints. Because of the study’s design — including its relatively small sample size —robust statistical analyses of these endpoints was not considered appropriate. That is, mathematically, such analyses would be very unlikely to provide meaningful data.

IMU-838 was generally safe and well tolerated in the study, Immunic stated. An adverse event was reported in about 42.9% of people receiving IMU-838 and 43.5% in those given a placebo. There were a total of three serious adverse events among patients in the treatment groups and one serious adverse event in a person in the placebo group.

Rates of treatment discontinuation in the 24-week period were similar in among patients given IMU-838 (5%) and those given placebo (7.2%). No abnormal laboratory tests of liver or kidney function were reported.

Analyses are ongoing and detailed trial results will be presented at upcoming scientific meetings, Immunic stated.

“Patients in the EMPhASIS trial exhibited robust responses across all study endpoints included in the top-line analysis,” Muehler said. “In addition to showing consistent activity by IMU-838 in RRMS using different measures, the study data also supports the previously observed favorable safety and tolerability profile of IMU-838 in RRMS patients.”

“Given the strength of these top-line results,” added Daniel Vitt, PhD, Immunic’s president and CEO, “we will continue to prepare a clinical phase 3 program for IMU-838 in RRMS and, after a full review of the data, anticipate providing a further update on development strategy.”

IMU-838 is also being investigated as a potential treatment for other diseases where an overactive immune system is thought to cause damage, including ulcerative colitis (a type of inflammatory bowel disease), primary sclerosing cholangitis and the coronavirus known as COVID-19.