PMID- 37905526 OWN - NLM STAT- MEDLINE DCOM- 20231130 LR - 20231216 IS - 1477-0970 (Electronic) IS - 1352-4585 (Print) IS - 1352-4585 (Linking) VI - 29 IP - 14 DP - 2023 Dec TI - Diroximel fumarate in patients with relapsing-remitting multiple sclerosis: Final safety and efficacy results from the phase 3 EVOLVE-MS-1 study. PG - 1795-1807 LID - 10.1177/13524585231205708 [doi] AB - 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. FAU - Singer, Barry A AU - Singer BA AD - The MS Center for Innovations in Care, Missouri Baptist Medical Center, St Louis, MO, USA. FAU - Arnold, Douglas L AU - Arnold DL AUID- ORCID: 0000-0003-4266-0106 AD - Montreal Neurological Institute, McGill University, Montreal, QC, Canada. AD - NeuroRx Research Inc., Montreal, QC, Canada. FAU - Drulovic, Jelena AU - Drulovic J AUID- ORCID: 0000-0002-4516-3458 AD - Clinic of Neurology, University of Belgrade, Belgrade, Serbia. FAU - Freedman, Mark S AU - Freedman MS AD - University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada. FAU - Gold, Ralf AU - Gold R AD - Department of Neurology, Ruhr University Bochum, Bochum, Germany. FAU - Gudesblatt, Mark AU - Gudesblatt M AD - NYU Langone South Shore Neurologic Associates, Patchogue, NY, USA. FAU - Jasinska, Elzbieta AU - Jasinska E AUID- ORCID: 0000-0003-0016-9896 AD - Collegium Medicum UJK, and Clinical Center, RESMEDICA, Kielce, Poland. FAU - LaGanke, Christopher C AU - LaGanke CC AD - North Central Neurology Associates, Cullman, AL, USA. FAU - Naismith, Robert T AU - Naismith RT AUID- ORCID: 0000-0003-0520-4283 AD - Washington University School of Medicine, St Louis, MO, USA. FAU - Negroski, Donald AU - Negroski D AD - MS Center of Sarasota, Sarasota, FL, USA. FAU - Oh, Jiwon AU - Oh J AUID- ORCID: 0000-0001-5519-6088 AD - Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. FAU - Hernandez Perez, Miguel Angel AU - Hernandez Perez MA AD - Hospital Universitario Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Spain. FAU - Selmaj, Krzysztof AU - Selmaj K AD - Center of Neurology, Lodz, Poland. AD - Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland. FAU - Then Bergh, Florian AU - Then Bergh F AD - Department of Neurology, University of Leipzig, Leipzig, Germany. FAU - Wundes, Annette AU - Wundes A AD - Department of Neurology, University of Washington Medical Center, Seattle, WA, USA. FAU - Ziemssen, Tjalf AU - Ziemssen T AUID- ORCID: 0000-0001-8799-8202 AD - Center of Clinical Neuroscience, Carl Gustav Carus University Hospital, Dresden, Germany. FAU - Castro-Borrero, Wanda AU - Castro-Borrero W AUID- ORCID: 0009-0002-9018-4263 AD - Biogen, Cambridge, MA, USA. FAU - Chen, Hailu AU - Chen H AD - Biogen, Cambridge, MA, USA. FAU - Levin, Seth AU - Levin S AD - Biogen, Cambridge, MA, USA. FAU - Scaramozza, Matthew AU - Scaramozza M AD - Biogen, Cambridge, MA, USA. FAU - Shankar, Sai L AU - Shankar SL AD - Biogen, Cambridge, MA, USA. FAU - Wang, Ting AU - Wang T AD - Biogen, Cambridge, MA, USA. FAU - Wray, Sibyl AU - Wray S AD - Hope Neurology MS Center, Knoxville, TN, USA. LA - eng PT - Journal Article DEP - 20231031 PL - England TA - Mult Scler JT - Multiple sclerosis (Houndmills, Basingstoke, England) JID - 9509185 RN - 0 (diroximel fumarate) RN - 0 (Immunosuppressive Agents) RN - FO2303MNI2 (Dimethyl Fumarate) SB - IM MH - Adult MH - Humans MH - *Multiple Sclerosis, Relapsing-Remitting/drug therapy MH - Immunosuppressive Agents/adverse effects MH - *Multiple Sclerosis/drug therapy MH - Dimethyl Fumarate/adverse effects MH - Recurrence PMC - PMC10687803 OTO - NOTNLM OT - Diroximel fumarate OT - clinical trial OT - disease-modifying therapy OT - efficacy OT - multiple sclerosis OT - relapsing-remitting multiple sclerosis OT - safety OT - tolerability COIS- Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BAS: research grant support from AbbVie, Biogen, Bristol Myers Squibb, Greenwich Biosciences, Novartis, and Sanofi and consulting and/or speaking fees from Alexion, Biogen, Bristol Myers Squibb, Cigna, Cycle, EMD Serono, Genentech, Horizon, Janssen, Novartis, Octave Bioscience, Roche, Sanofi, and TG Therapeutics.DLA: consulting fees from Albert Charitable Trust, Alexion Pharma, Biogen, Celgene, Frequency Therapeutics, Genentech, Med-Ex Learning, Merck, Novartis, Population Council, Receptos, Roche, and Sanofi-Aventis; grants from Biogen, Immunotec, and Novartis; and equity interest in NeuroRx.JD: advisory boards for Amicus, Biogen, Janssen, Medis, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva; speaker bureaus for Biogen, Bayer, Hemofarm, Janssen, Medis, Medtronic, Merck, Novartis, Roche, Sanofi-Genzyme, Teva, and Zentiva; and research grant from Roche.MSF: research/educational grants from Sanofi-Genzyme; honoraria/consultation fees from Alexion/AstraZeneca, BMS (Celgene), EMD Serono, Hoffman La-Roche, Actelion/Janssen (J&J), Novartis, Quanterix, Sanofi-Genzyme, and Teva Canada Innovation; advisory boards/boards of directors for Alexion/AstraZeneca, Atara Biotherapeutics, Bayer Healthcare, Celestra Health, Hoffman La-Roche, Actelion/Janssen (J&J), EMD Serono/Merck Serono, Novartis, and Sanofi-Genzyme; and participated in speakers bureau for Sanofi-Genzyme and EMD Serono.RG: research support and speaker's honoraria from Bayer-Schering, Biogen Idec, BMS, Chugai, Eisai, Genesis, Janssen, Merck Serono, Nikkiso Pharma, Novartis, Roche, Sanofi-Genzyme, Sandoz, and Teva; consulting honoraria from ZLB Behring, Baxter, Roche, and Talecris; and personal stock options in Bayer, Merck, and Roche.MG: consulting fees from Biogen, EMD Serono, Novartis, and Sanofi-Genzyme; research support from Alkermes; and speaker bureaus for Biogen, EMD Serono, Genentech-Roche, and Sanofi-Genzyme.EJ: advisory boards for Biogen and speaker fees from Biogen, Novartis, Roche, and Sanofi.CLG: consultant/advisory boards/speaker bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, Novartis, Sanofi-Genzyme, and TG Therapeutics.RTN: consultant for Abata Therapeutics, Banner Life Sciences, BeiGene, Biogen, Bristol Myers Squibb, Genentech, Genzyme, GW Therapeutics, Janssen, Horizon Therapeutics, Lundbeck, NervGen, and TG Therapeutics.DN: research support from and consultant/advisory boards/speaker bureaus for Adamas, Alkermes, Alexion, Bayer, Biogen, Celgene/BMS, EMD Serono, Janssen, Novartis, Roche-Genentech, and Sanofi-Genzyme.JO: research support from Biogen Idec, EMD Serono, and Roche and personal compensation for consulting/speaking from Biogen Idec, BMS, EMD Serono, Eli Lilly, Roche, Sanofi-Genzyme, and Novartis.MAHP: consultant/advisory boards/speaker bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Janssen, Novartis, Sanofi-Genzyme, and TG Therapeutics.KS: research support from Merck; advisory boards for Biogen, Celgene/BMS, Merck, Novartis, Roche, Sanofi, and TG Therapeutics.FTB: research support and travel grants, through his institution, from the German Science Fund (DFG), German Federal Ministry of Education and Science (BMBF), Bayer-Schering, Merck, Novartis, Pfizer, Roche, Sanofi, and Teva and speaker fees from and advisory boards for Actelion, Alexion, Bayer, Biogen, CSL Behring, Fresenius, Horizon, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva.AW: adviser fees from AbbVie and research support from AbbVie, Alkermes, and Biogen.TZ: personal compensation for consulting services and speaker honoraria from Bayer, Biogen Idec, Novartis, Sano fi , Synthon, and Teva and fi nancial support for research activities from Bayer, Biogen Idec, Novartis, Sanofi-Aventis, and Teva.WC-B, HC, SL, MS, SLS, and TW: employees of and hold stock/stock options in Biogen.SW: consulting fees from and advisory boards for Biogen, Celgene, and EMD Serono; speaker bureaus for Biogen, Celgene, EMD Serono, Roche-Genentech, and Sanofi-Genzyme; and research support from Biogen, Celgene, EMD Serono, Novartis, Receptos, Roche-Genentech, Sanofi-Genzyme, and TG. EDAT- 2023/10/31 12:41 MHDA- 2023/11/30 06:43 PMCR- 2023/11/30 CRDT- 2023/10/31 07:13 PHST- 2023/11/30 06:43 [medline] PHST- 2023/10/31 12:41 [pubmed] PHST- 2023/10/31 07:13 [entrez] PHST- 2023/11/30 00:00 [pmc-release] AID - 10.1177_13524585231205708 [pii] AID - 10.1177/13524585231205708 [doi] PST - ppublish SO - Mult Scler. 2023 Dec;29(14):1795-1807. doi: 10.1177/13524585231205708. Epub 2023 Oct 31.