Lower vidofludimus calcium dose not as effective in RRMS trial

A lower dose of the experimental oral therapy vidofludimus calcium (IMU-838) was not as effective as higher doses at reducing lesions in people with relapsing-remitting multiple sclerosis (RRMS), extended data from the therapy’s Phase 2 EMPhASIS trial show.

“We found that doses of 30 mg and 45 mg, but not 10 mg, suppressed new MRI brain lesions after 24 weeks when compared with placebo,” researchers wrote.

The results were announced in a paper titled, “Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis: Extended Results of a Placebo-Controlled Phase 2 Trial,“published in Neurology, Neuroimmunology and Neuroinflammation,

The trial was sponsored by Immunic Therapeutics, the company developing vidofludimus calcium.

“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, CEO and president of Immunic, said in a company press release.

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Vidofludimus calcium is designed to reduce multiple sclerosis (MS) inflammation by blocking the activity of an immune cell protein called DHODH. Recent evidence suggests also the therapy may exert nerve-protecting effects by activating a nerve protein called Nurr1.

As most available treatments for MS work only to reduce inflammation, vidofludimus calcium’s ability to simultaneously target inflammation and boost neuroprotection holds “the promise of delivering the therapeutic effects crucial to address the so far unmet medical needs for people living with MS,” Andreas Muehler, MD, chief medical officer of Immunic, said in an email to Multiple Sclerosis News Today.

The Phase 2 EMPhASIS trial (NCT03846219) tested vidofludimus calcium against a placebo in 268 adults with RRMS. In the first part of the study, participants were randomly assigned to take placebo or vidofludimus calcium at one of two doses — 30 mg or 45 mg — for about six months.

The trial’s main goal was to assess whether the therapy could reduce the total number of active lesions relative to a placebo, and results showed reductions with both doses — by 76% with the 30 mg dose and 71% with the 45 mg dose.

For perspective, the mean total number of active lesions after six months were 1.4 and 1.7 with both doses of vidofludimus, compared with an average of 5.8 lesions among those given a placebo.

Because there was no apparent difference in efficacy between the two tested doses, the EMPhASIS trial was expanded to include a second group of patients who were randomly assigned to take placebo or a lower dose (10 mg) of vidofludimus calcium.

After six months, the average number of active lesions in patients given 10 mg vidofludimus calcium was 5.9, which represents an increase of about 2% compared with placebo, and overall suggested this dose was not effective for reducing lesions.

Participants given any dose of vidofludimus calcium had fewer relapses per year compared with a placebo, and also about two times fewer disability progression events after six months (1.6% vs. 3.7%).

Biomarker analyses showed that neurofilament light chain (NfL) blood levels, a marker of nerve damage, decreased in a dose-dependent manner with vidofludimus calcium. This meant that NfL levels dropped by 17 picograms (pg)/mL with the 30 mg dose, and even more pronouncedly in patients given the highest dose (by 20.5 pg/mL).

The company had already shown that these reductions in NfL levels were observed even in patients who had no evidence of inflammatory MS activity — meaning no new or enlarging lesions and no relapses — supporting the drug’s neuroprotective effects in these patients.

Vitt said the findings “impressively underline the drug’s combined neuroprotective and anti-inflammatory effects.”

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Neuroprotective potential

Muehler said the MS therapy landscape “may appear crowded at a first view,” but “a critical unmet need still exists, as most available therapies are strictly anti-inflammatory drugs.”

“The progression of smoldering disease ongoing throughout the disease, relapse-independent disability worsening, and brain atrophy persist — insufficiently addressed by current inflammatory treatments — in both relapsing MS and progressive MS,” Muehler said. “This is the particular area where the excitement for vidofludimus calcium’s neuroprotective potential truly arises.”

Safety data from EMPhASIS showed vidofludimus calcium was generally well tolerated. About one in 10 patients given vidofludimus experienced side effects related to the therapy, but none of these was deemed serious. Three patients on the 45 mg dose chose to discontinue treatment due to side effects (one due to rash and two due to signs of liver damage on lab tests).

Collectively, the data indicate that 30 mg per day is the optimal dose of vidofludimus calcium for further testing, the researchers concluded.

Immunic is currently running two Phase 3 trials, ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638), to test the therapy in people with relapsing MS, including RRMS and active secondary progressive MS (SPMS). Both trials are enrolling patients at sites worldwide.

According to Vitt, Immunic expects to run a futility analysis toward the end of 2024. This type of analysis looks at available data from the trial to make sure it’s possible the study could have positive results. Top-line results from the studies are expected in the first half of 2026.

Immunic is also developing the therapy as a potential treatment for progressive forms of MS. A Phase 2 study called CALLIPER (NCT05054140) is testing vidofludimus calcium against a placebo in people with primary progressive MS, as well as active and nonactive SPMS.

A recent analysis also indicated the therapy reduced NfL levels in this population, again including patients with nonactive disease, consistent with early findings from EMPhASIS.