Progressive MS trial of vidofludimus calcium fully enrolled

A global Phase 2 clinical trial investigating the oral therapy vidofludimus calcium (IMU-838) in people with progressive forms of multiple sclerosis (MS) has reached full enrollment, the treatment’s developer, Immunic Therapeutics, reports.

Called CALLIPER (NCT05054140), the trial is assessing whether the neuroprotective effects of vidofludimus calcium seen in people with relapsing-remitting MS (RRMS) also extend to those with primary progressive MS (PPMS) or secondary progressive MS (SPMS).

“Our phase 2 CALLIPER trial is designed to corroborate the neuroprotective potential of vidofludimus calcium in a progressive patient population. Enrollment of the final [progressive MS] patient, according to plan, is another important milestone in the clinical development of our lead asset in MS,” Daniel Vitt, PhD, CEO and president of Immunic, said in a company press release.

“The neuroprotective properties of vidofludimus calcium were already identified in our phase 2 EMPhASIS trial … in relapsing-remitting MS, by showing an initial signal for prevention of confirmed disability worsening,” added Andreas Muehler, MD, the company’s chief medical officer.

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The company plans to share data from a first interim analysis in the coming months. This analysis will include biomarker data, such as changes with treatment versus a placebo in neurofilament light chain (NfL), a marker of nerve damage. Data will be collected from the first half of patients — about 225 people — who reached six months of follow-up.

Top-line data from the full group of 467 patients is expected in April 2025.

“We look forward to reporting the interim analysis of our CALLIPER trial, expected in the fall of this year, to assess biomarkers that have been shown in third-party research to consistently correlate with disease activity in neurodegenerative disorders,” Muehler said.

Vidofludimus calcium is an oral therapy designed to slow MS progression by interfering with the normal metabolism of immune cells that drive inflammation and cell death in MS. It works by blocking the dihydroorotate dehydrogenase (DHODH) enzyme, which is involved in the activation of such immune cells.

While this mechanism is shared with that of the approved therapy Aubagio (teriflunomide), vidofludimus calcium exerts neuroprotective effects that have not been observed with the older drug — possibly because it potently activates a protein called Nurr1.

Most commonly found in nerve cells, Nurr1 has neuroprotective and anti-neuroinflammatory activity, and it is an emerging therapeutic target for neurodegenerative diseases such as MS, Parkinson’s, and Alzheimer’s.

“In preclinical testing, we have discovered strong Nurr1 [activation] by vidofludimus calcium. The known characteristics of Nurr1 activation suggest broad therapeutic potential in neurodegenerative pathologies including MS,” Muehler said.

Trial enrolled 467 patients with PPMS and active or nonactive SPMS

CALLIPER has enrolled 467 patients with either PPMS or active or nonactive SPMS at more than 70 sites across North America, and Western, Central and Eastern Europe.

All participants were without evidence of relapses in the past two years, and they have been randomly assigned to a placebo or to 45 mg of vidofludimus calcium for up to 120 weeks, or about 2.5 years. After that, patients will have the option to enter an open-label extension period, where all will receive vidofludimus calcium for up to eight years.

The trial’s main goal is to assess if vidofludimus calcium can slow the annual rate of brain shrinkage over the 120 weeks compared with a placebo. Secondary measures include changes in brain volume over the first 24 weeks (about six months), and whether the treatment extends the time to confirmed disability progression.

CALLIPER is running in parallel with two twin Phase 3 studies — ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) — which are further evaluating the safety, tolerability, and effectiveness of the experimental therapy in adults with RRMS.

“Data from the CALLIPER trial, along with that from our ENSURE program, in conjunction with vidofludimus calcium’s postulated neuroprotective effects … may further strengthen the uniqueness of this treatment approach compared to other oral MS medications,” Vitt said.