Vidofludimus calcium trials continue as planned after panel review
Data monitoring committee deems trials worth continuing
An independent data monitoring committee has recommended that the twin ENSURE Phase 3 trials testing vidofludimus calcium in people with relapsing forms of multiple sclerosis (MS) continue as planned without adjustments.
The opinion that the trials are worth continuing was based on a review of interim, unblinded trial data, meaning the committee could see which patients got vidofludimus calcium and which received a placebo. The panel also indicated that there’s no need to enroll additional participants beyond what was originally planned.
As the studies move forward, they’re on track to finish in 2026, according to developer Immunic Therapeutics.
“I am particularly excited about the positive outcome of the interim analysis of our phase 3 ENSURE trials, marking the successful achievement of a critical milestone for the program,” Daniel Vitt, PhD, CEO of Immunic, said in a company press release.
‘Straightforward path’
“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 [relapsing MS],” Vitt said.
The identically designed ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) trials are each expected to enroll around 1,050 adults with active, relapsing forms of MS, including relapsing-remitting MS and active secondary progressive MS, at sites worldwide. For those interested, Immunic has created a website to help potential participants connect with these trials.
Vitt said the next major clinical milestone for vidofludimus calcium is top-line data from the ongoing Phase 2 CALLIPER trial (NCT05054140) that’s testing the oral treatment candidate in people with progressive forms of MS. That readout is expected in April 2025.
Vidofludimus calcium is an oral small molecule that works to reduce MS-related inflammation by blocking a protein called DHODH that’s important for immune cell metabolism. Evidence also suggests the treatment may activate a protein called Nurr1 to exert neuroprotective effects.
In ENSURE-1 and ENSURE-2, participants are being randomly assigned to receive oral vidofludimus calcium (30 mg) or a placebo once daily for up to 72 weeks (1.5 years). Those who complete the main trial will be given the option to enter an open-label extension, in which all will receive vidofludimus calcium for up to eight years.
The main goal is to evaluate the time to the first MS relapse, with secondary goals including measures of disability, brain lesions, cognition, and brain tissue volume.
A futility analysis from the IDMC was planned for when about half of the planned first relapse events had occurred in the main part of both trials.
Futility analyses aim to determine whether a study should be stopped early because it’s very unlikely to achieve its goals. They can also help decide whether additional participants need to be enrolled in the study in order to see a meaningful treatment effect.
The committee determined that futility criteria in the ENSURE trials were not met, so the trial should continue, and that the number of planned participants did not need to be adjusted.
Immunic hasn’t seen the unblinded data so that it can remain unbiased until the trial is complete.
“While Immunic remains blinded to all data, the IDMC’s favorable recommendations in this interim analysis corroborate our initial assumptions … and suggest that they are in line with the data observed so far,” said Andreas Muehler, MD, Immunic’s chief medical officer.
In CALLIPER, which is fully enrolled, about 450 adults with primary progressive MS or SPMS without evidence of relapses in the last two years were randomly assigned to receive daily oral vidofludimus calcium (45 mg) or a placebo for 120 weeks, or a little over two years.
That trial’s main goal is to evaluate changes in the rate of brain volume loss, with secondary goals including measures of disability and safety. As with the ENSURE studies, CALLIPER will be followed by an open-label extension period of up to eight years.
Early data from CALLIPER 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.
“If this data set continues to show a neuroprotective effect for vidofludimus calcium, we believe our drug may be positioned as first-in-class oral treatment option for [progressive MS], a form of MS with highest unmet medical needs,” Vitt said.
About the Author
