Vumerity

The pathophysiology of multiple sclerosis (MS) is multifaceted and propagated through ongoing inflammatory and neurodegenerative stimuli, mediated at least in part by toxic oxidative stress. Preclinical studies indicate that diroximel fumarate pharmacodynamic responses appear to be mediated, at least in part, through activation of the nuclear factor (erythroid derived 2) like 2 (Nrf2) transcriptional pathway, which is the primary cellular defense system for responding to a variety of potentially toxic stimuli through up regulation of antioxidant response genes. Dimethyl fumarate reduces inflammatory responses in both peripheral and central cells and promotes cytoprotection of central nervous system cells against toxic oxidative damage, demonstrating effects on pathways known to exacerbate MS pathology. Dimethyl fumarate has also been shown to up regulate Nrf2 dependent antioxidant genes in patients, confirming clinical pharmacodynamic activity in humans. Vumerity and dimethyl fumarate undergo rapid hydrolysis prior to systemic circulation by esterases and are converted to the primary active metabolite, mycophenolate mofetil (MMF). However, the mechanism by which Vumerity and dimethyl fumarate exert therapeutic effects in MS is not fully understood.