Diroximel fumarate (Vumerity®) capsules have recently been added to the Pharmaceutical Benefits Scheme (PBS) for clinically definite relapsing-remitting multiple sclerosis (MS). The clinical criteria require patients to be ambulatory and not be taking any other PBS-subsidised disease-modifying therapy for MS.

The action of diroximel fumarate appears to be related to activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. This pathway is involved in the cellular response to oxidative stress. As increased production of reactive oxygen species is implicated in the pathogenesis of MS, the Nrf2 pathway has emerged as a new therapeutic target.

Diroximel fumarate is rapidly converted to its active metabolite, monomethyl fumarate (MMF). This is also the active metabolite of dimethyl fumarate (Tecfidera®). Therefore, once metabolised, diroximel fumarate and dimethyl fumarate are expected to have a similar adverse effect profile. The EVOLVE-MS-2 Study investigated the gastrointestinal effects of the two agents and found diroximel fumarate to be significantly better tolerated than dimethyl fumarate. Fewer patients in the diroximel fumarate group discontinued treatment due to adverse effects (1.6% versus 5.6%), with this difference largely due to gastrointestinal tolerability.

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