To report interim safety and efficacy outcomes with diroximel fumarate (DRF) from EVOLVE-MS-1.

DRF is an oral fumarate for relapsing multiple sclerosis (MS). DRF has the same active metabolite as dimethyl fumarate (DMF) and is expected to have a similar efficacy/safety profile. DRF has improved gastrointestinal (GI) tolerability vs DMF.

EVOLVE-MS-1 (NCT02634307) is an ongoing, open-label, 96-week study assessing DRF safety, tolerability, and efficacy in adults with relapsing-remitting MS (RRMS). Patients were either newly enrolled in EVOLVE-MS-1 or enrolled after completing EVOLVE-MS-2 (NCT03093324), a randomized, blinded, phase 3, 5-week study of DRF or DMF treatment.

As of September 1, 2020, 1057 patients were enrolled, 464 had completed EVOLVE-MS-2. Median DRF exposure was 2.0 (range 0.0–2.1) years. Overall, 23.3% (246/1057) of patients discontinued treatment; 8.0% (85/1057) due to adverse events (AEs) and <1% (7/1057) due to GI AEs. AEs occurred in 88.2% (932/1057) of patients; 89% (834/932) were mild/moderate in severity. GI AEs occurred in 31.6% (334/1057) of patients. GI AEs and discontinuation due to GI AEs in newly enrolled patients was 33.7% (200/593) and 0.8% (5/593), respectively. Adjusted annualized relapse rate was 0.13 (95% CI 0.11–0.15) overall, an 81% (95% CI 78.1–84.1; p<0.0001) reduction from 12 months prior (0.70 [95% CI 0.66–0.75]). At Week 96, estimated proportion of relapse-free patients was 82.4%. Percentage of Gd+ lesion-free patients was 69.0% at baseline vs 91.2% at Week 96. Mean number of new/newly enlarging T2 lesions remained stable or declined slightly from Year 1 to Year 2.

At 2 years, safety, clinical, and radiological measures were reduced from baseline, supporting DRF as an effective treatment option and consistent with the known benefit-risk profile for DMF. The low rate of treatment discontinuation over 2 years suggests DRF is a well-tolerated treatment option for RRMS.

Study Supported by: Biogen