Monomethyl Fumarate (Bafiertam): A Comprehensive Pharmacological and Clinical Review

1.0 Executive Summary & Overview

Monomethyl Fumarate (MMF), commercially available as Bafiertam®, is an orally administered disease-modifying therapy (DMT) approved by the United States Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS) in adult patients.[1] This small molecule represents a significant and logical evolution within the fumarate class of therapeutics. It is the direct, pharmacologically active metabolite of the widely prescribed prodrugs dimethyl fumarate (DMF), marketed as Tecfidera®, and diroximel fumarate (DRF), marketed as Vumerity®.[3] The development of this direct-delivery formulation was predicated on achieving bioequivalence with its parent prodrugs while aiming to provide an improved gastrointestinal (GI) tolerability profile, which has been a notable clinical challenge limiting the use of earlier fumarate therapies in some patients.[7]

The therapeutic effects of MMF are understood to be multifactorial, with the primary mechanism of action being the activation of the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcriptional pathway.[5] This pathway serves as a master regulator of the cellular response to oxidative stress, a fundamental pathological driver in the neuroinflammatory and neurodegenerative cascade of multiple sclerosis.[12] Beyond its potent antioxidant effects, MMF exerts broad immunomodulatory properties, including the capacity to shift the systemic immune response toward a more anti-inflammatory state and inhibit the migration of pathogenic immune cells across the blood-brain barrier into the central nervous system (CNS).[12]