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.
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.
The speaker expresses a degree of skepticism, particularly regarding the proposed neuroprotective mechanism involving the NURR1 receptor. He notes that genome-wide association studies show no link between gene variants of NURR1 and MS, and that MS risk genes are primarily related to the immune system, suggesting the NURR1 aspect might be a "red herring." While he acknowledges the potential value of reducing disability progression in progressive MS, even by 20-30% with low side effects, he is not convinced of the NURR1 receptor's role. He also expresses doubt about the inclusion of the 15mg dose in the Phase 3 trials, given the 10mg dose's poor performance in Phase 2.
The video mentions several potential side effects associated with Vidofludimus Calcium. In the Phase 2 trial, serious adverse events in the 30mg group included squamous cell carcinoma of the cervix, a bone fracture, and kidney stone/nephritis. In the 45mg group, three participants stopped the drug due to elevated liver enzymes (two people) or rash (one person). These liver issues resolved on their own. The CALIPER trial for progressive MS showed slightly more serious adverse events in the treatment group compared to placebo. Specific side effects mentioned include pyelonephritis (kidney infection), vertigo, and potential liver function test elevations, although the extent of milder elevations is not detailed. The speaker also suggests that side effects common to Aubagio, another DHODH inhibitor, might occur, such as elevated liver function tests, loose stools, nausea, hair thinning, neuropathy, and infections.
Vidofludimus Calcium has been associated with several potential side effects across the trials discussed.
In the Phase 2 trial for relapsing MS, serious adverse events were noted in the 30mg group, including squamous cell carcinoma of the cervix, a bone fracture, and kidney stone/nephritis. In the 45mg group of this trial, three participants discontinued the medication: two due to elevated liver enzymes and one due to a rash. The liver abnormalities resolved spontaneously after stopping the drug.
For the CALIPER trial investigating progressive MS, the overall rate of adverse events was similar to placebo. However, serious adverse events were slightly higher in the Vidofludimus Calcium group (8.1%) compared to placebo (6.5%). Specific side effects mentioned include pyelonephritis (kidney infection), though this was also reported in the placebo group, and vertigo, which occurred in the treatment group but not the placebo group. While milder elevations in liver function tests were not detailed, the speaker suggested that side effects commonly seen with Aubagio, another drug targeting the DHODH enzyme, might also occur with Vidofludimus Calcium. These include elevated liver function tests, loose stools, nausea, hair thinning, neuropathy, and infections. No deaths were reported in the Phase 2 study.
