Objective:

To assess safety, tolerability, and efficacy of diroximel fumarate (DRF) in male patients compared with female patients in EVOLVE-MS-1.

Background:

Males with relapsing multiple sclerosis (RMS) have lower incidence (1:3), higher risk for poor prognosis, and faster disease progression than females. DRF is an oral fumarate for RMS with the same active metabolite as dimethyl fumarate (DMF). DRF is expected to have a safety/efficacy profile similar to DMF but demonstrated fewer gastrointestinal (GI)-related adverse events (AEs).

Design/Methods:

EVOLVE-MS-1 (NCT02634307) is a 2-year, phase 3 study of DRF in adults with RMS. Patients either entered as newly enrolled to DRF trials, or from the 5-week, randomized, head-to-head, double-blind, phase 3 EVOLVE-MS-2 study (NCT03093324) of DRF and DMF.

Results:

As of Jan-2022, 1057 patients (male, n=295; female, n=762) were enrolled. Baseline characteristics were generally similar between male and female patients. Overall, 7% of males and 8% of females discontinued treatment due to AEs. AEs occurred in 86% of males and 90% of females; serious AEs occurred in 15% and 11%, respectively. In males and females, GI AEs occurred in 29% and 33%, and flushing AEs occurred in 22% and 29%, respectively. Adjusted annualized relapse rate was 0.13 in both males (95% CI: 0.10-0.19) and females (95% CI: 0.11-0.15; 82.4% and 81.2% reductions vs 12 months before study entry, respectively [both p<0.0001]). Proportions of patients who were Gd+ lesion-free at Week 96 vs Baseline, respectively, were 88.1% vs 69.4% (males) and 92.3% vs 70.8% (females). Estimated proportions of patients free from confirmed disability progression at 96 weeks were similar: males, 90.7%; females, 90.0%.

Conclusions:

After 2 years of DRF exposure, both male and female patients with MS had similar safety, tolerability, and efficacy outcomes. These data suggest that, despite males tending to experience more aggressive disease, DRF is a suitable treatment strategy for this patient cohort.