Immunic Therapeutics is advancing Vidofludimus calcium (IMU-838), an oral small molecule drug, as a potential treatment for chronic inflammatory and autoimmune diseases, particularly multiple sclerosis (MS). The drug's selectivity and favorable safety profile, comparable to placebo, offer a promising alternative to traditional immunosuppressants, which often carry significant side effects.
Targeting Autoimmune Diseases with Precision
Vidofludimus calcium targets dihydroorotate dehydrogenase (DHODH), an enzyme crucial for metabolically activated immune cells involved in autoimmune diseases. Unlike broad immunosuppressants, Vidofludimus calcium selectively inhibits the harmful activity of the immune system without compromising its ability to fight infections or cancers. Preclinical data also indicate that Vidofludimus calcium activates the neuroprotective transcription factor nuclear receptor related 1 (Nurr1), potentially enhancing its benefits for patients by directly protecting neurons.
Clinical Trial Highlights
Data presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 highlighted several key aspects of Vidofludimus calcium's potential in MS treatment. Interim analysis from the Phase II CALIPER trial in progressive MS demonstrated a noticeable reduction in neurofilament light chain, a biomarker of neuronal damage, compared to placebo. This effect was consistent across different patient subgroups, suggesting broad efficacy across all progressive MS subtypes.
Another study linked the reduction of Epstein-Barr Virus (EBV) reactivations with potential alleviation of MS-related fatigue, a common and debilitating symptom. Vidofludimus calcium is being investigated as a potential symptomatic therapy for MS fatigue in ongoing trials. Further research explored neuroprotective mechanisms related to Nurr1 activation, showing that Vidofludimus calcium protects neurons by reducing the activity of microglial cells and improving the neurotoxic environment around nerve cells. The drug also appears to reduce apoptosis, enhancing neuronal survival under stressful conditions.
Ongoing Phase III Trials
The definitive proof of Vidofludimus calcium's efficacy and safety hinges on the completion of Phase III studies. Immunic Therapeutics is currently conducting twin Phase III trials in relapsing multiple sclerosis. These trials focus on relapse activity, closely linked to magnetic resonance imaging (MRI) lesions, for which a statistically significant effect was already observed in the previous Phase II EMPhASIS trial in relapsing-remitting MS. In those trials, Vidofludimus calcium demonstrated a greater than 75 percent reduction in MRI lesions, correlating strongly with a reduction in relapses.
The Future of Oral Small Molecule Drugs
Oral small molecule drugs like Vidofludimus calcium are gaining prominence due to their ability to penetrate cells, opening new therapeutic avenues, particularly in the central nervous system. The pharmaceutical industry is increasingly focusing on inflammatory and autoimmune diseases, recognizing the significant unmet needs in these areas. The success of glucagon-like peptide 1 (GLP-1) agonists has also demonstrated the potential for small molecules to replicate similar effects, offering improved patient adherence and reduced healthcare costs.
