Vidofludimus calcium for the treatment of multiple sclerosis: development rationale, mechanism of action, and early trial data

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune condition of the central nervous system associated with progressive disability. Safe and well tolerated treatments targeting both inflammatory and neurodegenerative processes are needed to address the spectrum of MS pathophysiology. AREAS COVERED: Vidofludimus calcium is a potent, orally available direct activator of nuclear receptor-related 1 (Nurr1) protein and selective dihydroorotate dehydrogenase (DHODH) inhibitor. The article explores the chemistry, mechanisms of action, and pharmacokinetics of vidofludimus calcium. Furthermore, preliminary data from phase 2 trials are discussed. EXPERT OPINION: The mechanism of action of vidofludimus calcium may allow targeting of focal neuroinflammation as well as chronic-compartmentalized inflammation and neurodegeneration. Treatment with vidofludimus calcium in patients with relapsing-remitting MS resulted in a statistically significant reduction of magnetic resonance imaging lesions in the phase 2 EMPhASIS trial. In CALLIPER, a phase 2 trial in patients with progressive MS, preliminary reports indicate consistent trends on signals related to disability progression across different disability outcomes and subpopulations. Completed studies indicate that vidofludimus calcium was generally well tolerated. In light of current unmet treatment needs, results from ongoing phase 3 trials are awaited with interest.