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

Abstract

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.

• Authors: Barry A Singer, Douglas L Arnold, Jelena Drulovic, Mark S Freedman, Ralf Gold, Mark Gudesblatt, Elzbieta Jasinska, Christopher C LaGanke, Robert T Naismith, Donald Negroski, Jiwon Oh, Miguel Angel Hernandez Perez, Krzysztof Selmaj, Florian Then Bergh, Annette Wundes, Tjalf Ziemssen, Wanda Castro-Borrero, Hailu Chen, Seth Levin, Matthew Scaramozza, Sai L Shankar, Ting Wang, Sibyl Wray
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 29 Issue 14 Pg. 1795-1807 (Dec 2023) ISSN: 1477-0970 [Electronic] England
• PMID: 37905526 (Publication Type: Journal Article)

Chemical References

• diroximel fumarate
• Immunosuppressive Agents
• Dimethyl Fumarate

Topics

• Adult
• Humans
• Multiple Sclerosis, Relapsing-Remitting (drug therapy)
• Immunosuppressive Agents (adverse effects)
• Multiple Sclerosis (drug therapy)
• Dimethyl Fumarate (adverse effects)
• Recurrence