About this video

• Video Title: Vidofludimus Calcium for MS
• Channel: Dr. Brandon Beaber
• Speakers: Dr. Brandon Beaber
• Duration: 00:17:59

Overview

This video discusses Vidofludimus Calcium, an investigational drug for Multiple Sclerosis (MS). It explores its potential dual mechanisms of action (anti-inflammatory and neuroprotective), reviews Phase 2 trial results for relapsing MS and Phase 2b (CALIPER) trial results for progressive MS, and discusses potential side effects.

Key takeaways

• Vidofludimus Calcium is a small molecule drug being developed by Immunic, currently in Phase 3 trials for MS.
• It has two proposed mechanisms: inhibiting DHODH (similar to Aubagio) and activating the NURR1 receptor (for neuroprotection).
• Phase 2 trials showed efficacy in reducing gadolinium-enhancing lesions in relapsing MS at 30mg and 45mg doses, but no significant reduction in relapses or disability progression. Neurofilament light chain levels were reduced at these doses.
• The CALIPER Phase 2b trial in progressive MS (SPMS and PPMS) showed a 20% reduction in disability progression over approximately 2 years, with a more pronounced effect in those with primary progressive MS and those without active lesions. Brain atrophy was not significantly reduced.
• Side effects appear to be generally manageable and similar to placebo, though some serious adverse events were reported, and a few participants discontinued the drug due to elevated liver enzymes or rash.
• The presenter questions the relevance of the NURR1 mechanism due to a lack of genetic association with MS risk.

In the Phase 2 trial for relapsing MS, the overall rate of reported events was similar to placebo. There were rare serious adverse events in the 30mg group, including squamous cell carcinoma of the cervix, a bone fracture, and kidney stone/nephritis. Three participants in the 45mg group stopped the drug: two due to elevated liver enzymes and one due to a rash. These liver abnormalities resolved spontaneously.

In the CALIPER trial for progressive MS, the overall rate of adverse events was similar to placebo. Serious adverse events were slightly higher (8.1% vs. 6.5%). Reported events included pyelonephritis (kidney infection), with one case in the treatment group and one in the placebo group. Two participants experienced vertigo, compared to none in the placebo group. No participants had significant liver injury reported. The presenter notes a lack of data on milder elevations of liver function tests. The presenter also speculates that side effects seen with Aubagio, another DHODH inhibitor, such as elevated liver function tests, loose stools, nausea, hair thinning, neuropathy, and infections, could potentially occur with Vidofludimus Calcium.