To explore clinical and radiological disease outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with diroximel fumarate (DRF) in EVOLVE-MS-1.

DRF (formerly ALKS 8700; BIIB098) is a novel fumarate being developed for relapsing forms of MS. DRF is expected to have similar efficacy as dimethyl fumarate (both are converted to monomethyl fumarate), with the potential for a differentiated gastrointestinal tolerability profile.

EVOLVE-MS-1 (NCT02634307) is an ongoing, open-label, phase 3 study of DRF safety/tolerability over 96 weeks in patients with RRMS. Interim annualized relapse rate (ARR) and radiological endpoints were evaluated in the total safety population and in patients who received ≥1 dose and completed ≥1 post-baseline efficacy assessment, respectively. Newly diagnosed patients (≤1 year since MS diagnosis, no prior DMT) were also analyzed. 

As of March 30, 2018, median (range) duration of DRF exposure was 59.9 (0.1-98.9) weeks. ARR improved from baseline to Wk48 in the total safety population (baseline, 0.8; Wk48, 0.17; 79% reduction; n=696) and newly diagnosed patients (baseline, 1.1; Wk48, 0.20; 82% reduction; n=82). Estimated proportion of patients with a relapse at Wk48 was similar in both groups (total, 13.1%; newly diagnosed, 14.0%). From baseline to Wk48, mean (SD) number of GD+ lesions was reduced by 77% (baseline, 1.3 [4.33]; Wk48, 0.3 [1.56]; p<0.0001) in the total population (n=503) and 96% (baseline, 2.2 [6.20]; Wk48, 0.1 [0.38]; p=0.0051) in newly diagnosed patients (n=70). A greater percentage of patients in both groups had no Gd+ lesions at Wk48 versus baseline (total, 90.3% [454/503] vs 67.0% [337/503]; newly diagnosed, 88.6% [62/70] vs 55.7% [39/70]).

As of this interim data cut, DRF demonstrated treatment effect via clinical and radiological measures of disease activity. Newly diagnosed patients had notable improvements in ARR and Gd+ lesion count, highlighting the effectiveness of DRF in this population.

Supported by: Biogen/Alkermes