Immunic, Inc. has announced that its Phase 3 ENSURE program, investigating vidofludimus calcium for the treatment of relapsing multiple sclerosis (RMS), will continue as planned following a positive outcome from an interim futility analysis. The recommendation comes from an independent data monitoring committee (IDMC) after reviewing unblinded data from the ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) trials.
The ENSURE program consists of two identical, multicenter, randomized, double-blind Phase 3 trials designed to assess the efficacy, safety, and tolerability of vidofludimus calcium versus placebo in patients with RMS. Each trial aims to enroll approximately 1,050 adults with active RMS across more than 100 sites in over 15 countries. Participants are being randomized to receive either a 30 mg daily dose of vidofludimus calcium or a placebo for up to 72 weeks, with the primary endpoint being the time to first relapse.
The IDMC's interim futility analysis was based on a pre-specified assessment conducted after approximately half of the planned first relapse events had occurred in the double-blind treatment periods of both ENSURE-1 and ENSURE-2. The analysis was designed to inform potential sample size adjustments and ensure that the final study readout occurs after sufficient events have been recorded. The IDMC was tasked with determining whether the trials met futility criteria and whether the sample size should be increased. The committee concluded that futility criteria were not met and recommended that the trials continue without any changes.
Vidofludimus Calcium's Mechanism of Action
Vidofludimus calcium, also known as IMU-838, is an oral small molecule designed to reduce MS-related inflammation by blocking dihydroorotate dehydrogenase (DHODH), a protein important for immune cell metabolism. Evidence also suggests that the treatment may activate nuclear receptor related 1 (Nurr1) to exert neuroprotective effects.
CALLIPER Trial
In addition to the ENSURE program, vidofludimus calcium is being evaluated in the Phase 2 CALLIPER trial (NCT05054140) for progressive forms of MS. The trial, which is fully enrolled, includes approximately 450 adults with primary progressive MS or secondary progressive MS without recent relapses. Participants were randomized to receive either 45 mg of vidofludimus calcium or a placebo daily for 120 weeks. The primary goal of the CALLIPER trial is to assess changes in the rate of brain volume loss, with secondary goals including measures of disability and safety. Top-line data from the CALLIPER trial is expected in April 2025.
Prior Clinical Data
Early data from the CALLIPER trial indicated that vidofludimus calcium lowered levels of neurofilament light chain, a nerve damage biomarker, after six months of treatment, whereas levels increased over time for patients given a placebo. Data from the Phase 2 EMPhASIS trial in relapsing-remitting MS showed that 30-mg and 45-mg daily doses of vidofludimus calcium decreased the cumulative number of active lesions compared to placebo over 24 weeks.
Management Commentary
"While Immunic remains blinded to all data, the IDMC's favorable recommendations in this interim analysis corroborate our initial assumptions for the design, powering and relapse rate of the twin phase 3 trials of vidofludimus calcium in RMS, and suggest that they are in line with the data observed so far," said Andreas Muehler, MD, MBA, Chief Medical Officer of Immunic. Daniel Vitt, PhD, CEO of Immunic, added, "We are confident in vidofludimus calcium's potential to transform the oral MS market and continue to believe that the phase 3 program provides a clear and straightforward path towards seeking potential regulatory approval in RMS."
Trial Completion
Completion of ENSURE-1 is anticipated in the second quarter of 2026, with ENSURE-2 expected to be completed in the second half of 2026.
