Early data from twin late-stage MS drug trials expected by year’s end

Immunic says it’s on track to announce early data by year’s end from twin late-stage trials testing vidofludimus calcium (IMU-838) — an oral therapy believed to have both anti-inflammatory and neuroprotective properties — in people with relapsing forms of multiple sclerosis (MS).

The top-line results from the two Phase 3 trials, ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638), will help determine whether the experimental treatment can significantly extend the time to a first MS relapse, according to Immunic. If the results are positive, the developer plans to submit a new drug application to the U.S. Food and Drug Administration in mid-2027, with a potential approval targeted for 2028, the company said in a press release providing financial results and a corporate update.

“With regulatory alignment and precedent surrounding the time to first relapse primary endpoint [trial goal], the path to regulatory submission upon positive trial results is clear,” said Michael A. Panzara, MD, chief medical officer of Immunic. Panzara added that the “Phase 3 ENSURE trials of vidofludimus calcium in relapsing MS remain on track to report top-line data by the end of 2026.”

Building on findings from a Phase 2 trial dubbed  CALLIPER (NCT05054140) — which, according to Immunic, continue to suggest that vidofludimus calcium may address the mechanisms underlying disability progression in people with progressive forms of MS — Panzara said the company is also gearing up for clinical testing for that indication.

“We are preparing to initiate our Phase 3 progressive MS trial later this year, reinforcing our commitment to evaluating the potential of vidofludimus calcium for anyone living with MS,” Panzara said.

Recommended Reading

May 2, 2025 News by Margarida Maia, PhD

Vidofludimus calcium lowers risk of progressive MS disability worsening

Taken in trials as oral tablets, vidofludimus calcium is designed to simultaneously target inflammation and the mechanisms thought to contribute to nerve cell damage in MS. This is expected to address the acute inflammatory attacks that drive relapses — or periods of new or worsening symptoms — in people with relapsing forms of MS, as well as the chronic, low-grade inflammation and nerve cell death that drive gradual disability worsening across MS types.

The therapy’s potential in relapsing forms of MS was first explored in the EMPhASIS Phase 2 trial (NCT03846219), which enrolled more than 200 adults with relapsing-remitting MS (RRMS). Participants received vidofludimus calcium — at a dose of 10 mg, 30 mg, or 45 mg — or a placebo for about six months, after which all had the option to continue receiving or switch to the experimental therapy in an open-label extension.

Results from the main trial showed the higher doses reduced the total number of active lesions, namely new or enlarging areas of tissue damage and those with active inflammation, by more than 70% compared with the placebo. Use of vidofludimus calcium also led to fewer relapses and fewer disability progression events after six months.

Longer-term follow-up from EMPhASIS and its extension portion also suggested that the therapy’s effects may extend beyond reducing inflammatory disease activity. After nearly three years, more than 90% of participants remained free from confirmed disability worsening.

ENSURE trials tested vidofludimus calcium in over 2,000 adults

The ENSURE-1 and ENSURE-2 trials are now expected to confirm those findings in a larger group of people with relapsing forms of MS. The studies have together enrolled more than 2,000 adults with RRMS and active secondary progressive MS (SPMS). All are receiving 30 mg of vidofludimus calcium or a placebo for up to 72 weeks, or nearly 1.5 years.

The main goal or endpoint of both trials is to determine whether the therapy can delay the time to a first relapse, while secondary goals include assessments of its effects on lesions, disability progression, and cognition. Loss of brain volume, or brain atrophy), are also being assessed.

We believe [vidofludimus calcium] has the potential to deliver meaningful efficacy while maintaining the favorable safety and tolerability profile observed to date, positioning [it] as a potentially important new oral treatment option for people living with MS.

While the ENSURE trials are focused on relapsing forms of MS, Immunic is also pursuing vidofludimus calcium as a potential treatment for progressive forms of the disease. The mid-stage CALLIPER trial enrolled 467 adults with primary progressive MS or SPMS who received 45 mg vidofludimus calcium or a placebo for up to 120 weeks, or nearly 2.5 years.

While the trial failed to meet its main goal of showing that vidofludimus could slow brain atrophy, the treatment candidate significantly reduced the risk of confirmed disability worsening compared with a placebo. Importantly, this risk was reduced even in patients without signs of active inflammation on MRI scans, supporting the idea that therapy may act on more than inflammation alone.

After completing the main CALLIPER trial, participants could also enter an open-label extension and continue receiving vidofludimus calcium for as long as eight years. As of May, 340 participants were still being treated in the extension part, according to the developer.

“We remain highly encouraged by the consistent and differentiated profile of vidofludimus calcium,” said Jason Tardio, president and chief operating officer of Immunic. “We believe this approach has the potential to deliver meaningful efficacy while maintaining the favorable safety and tolerability profile observed to date, positioning vidofludimus calcium as a potentially important new oral treatment option for people living with MS.”