Diroximel fumarate in patients with relapsing–remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study

• Published in: Multiple sclerosis Vol. 29; no. 14; pp. 1795 - 1807
• Main Authors: Singer, Barry A, Arnold, Douglas L, Drulovic, Jelena, Freedman, Mark S, Gold, Ralf, Gudesblatt, Mark, Jasinska, Elzbieta, LaGanke, Christopher C, Naismith, Robert T, Negroski, Donald, Oh, Jiwon, Hernandez Perez, Miguel Angel, Selmaj, Krzysztof, Then Bergh, Florian, Wundes, Annette, Ziemssen, Tjalf, Castro-Borrero, Wanda, Chen, Hailu, Levin, Seth, Scaramozza, Matthew, Shankar, Sai L, Wang, Ting, Wray, Sibyl
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-12-2023; Sage Publications Ltd
• Subjects: Gadolinium; Multiple sclerosis; Original Research Papers; Safety; clinical trial; multiple sclerosis; safety; disease-modifying therapy; tolerability; relapsing–remitting multiple sclerosis; efficacy; Diroximel fumarate
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/13524585231205708

Background:
Diroximel fumarate (DRF) is approved for adults with relapsing–remitting multiple sclerosis (RRMS) in Europe and for relapsing forms of MS in the United States. DRF and dimethyl fumarate (DMF) yield bioequivalent exposure of the active metabolite monomethyl fumarate. Prior studies indicated fewer gastrointestinal (GI)-related adverse events (AEs) with DRF compared with DMF.
Objective:
To report final outcomes from EVOLVE-MS-1.
Methods:
EVOLVE-MS-1 was an open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in patients with RRMS. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory.
Results:
Overall, 75.7% (800/1057) of patients completed the study; median exposure was 1.8 (range: 0.0–2.0) years. AEs occurred in 938 (88.7%) patients, mostly of mild (28.9%) or moderate (50.3%) severity. DRF was discontinued due to AEs in 85 (8.0%) patients, with < 2% discontinuing due to GI or flushing/flushing-related AEs. At Week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (72.7%; p < 0.0001); adjusted annualized relapse rate was 0.13 (95% confidence interval: 0.11–0.15).
Conclusion:
DRF was generally well tolerated over 2 years, with few discontinuations due to AEs; radiological measures indicated decreased disease activity from baseline. These outcomes support DRF as a treatment option in patients with RRMS.