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

Author:

Singer Barry A1,Arnold Douglas L23ORCID,Drulovic Jelena4ORCID,Freedman Mark S5,Gold Ralf6,Gudesblatt Mark7,Jasinska Elzbieta8ORCID,LaGanke Christopher C9,Naismith Robert T10ORCID,Negroski Donald11,Oh Jiwon12ORCID,Hernandez Perez Miguel Angel13,Selmaj Krzysztof1415,Then Bergh Florian16,Wundes Annette17,Ziemssen Tjalf18ORCID,Castro-Borrero Wanda19ORCID,Chen Hailu19,Levin Seth19,Scaramozza Matthew19,Shankar Sai L19,Wang Ting19,Wray Sibyl20

Affiliation:

1. The MS Center for Innovations in Care, Missouri Baptist Medical Center, St Louis, MO, USA

2. Montreal Neurological Institute, McGill University, Montreal, QC, Canada

3. NeuroRx Research Inc., Montreal, QC, Canada

4. Clinic of Neurology, University of Belgrade, Belgrade, Serbia

5. University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada

6. Department of Neurology, Ruhr University Bochum, Bochum, Germany

7. NYU Langone South Shore Neurologic Associates, Patchogue, NY, USA

8. Collegium Medicum UJK, and Clinical Center, RESMEDICA, Kielce, Poland

9. North Central Neurology Associates, Cullman, AL, USA

10. Washington University School of Medicine, St Louis, MO, USA

11. MS Center of Sarasota, Sarasota, FL, USA

12. Division of Neurology, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

13. Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

14. Center of Neurology, Lodz, Poland

15. Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland

16. Department of Neurology, University of Leipzig, Leipzig, Germany

17. Department of Neurology, University of Washington Medical Center, Seattle, WA, USA

18. Center of Clinical Neuroscience, Carl Gustav Carus University Hospital, Dresden, Germany

19. Biogen, Cambridge, MA, USA

20. Hope Neurology MS Center, Knoxville, TN, USA

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.

Funder

Biogen

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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