January 7, 2020 Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study Annette Wundes, MD, is a neurologist who specializes in multiple sclerosis. Robert T Naismith, Washington University, School of Medicine, St. Louis, MO, USA Jerry S Wolinsky, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA Annette Wundes, Department of Neurology, University of Washington Medical Center, Seattle, WA, USA Christopher LaGanke, North Central Neurology Associates, Cullman, AL, USA Douglas L Arnold, Montreal Neurological Institute, McGill University, Montreal, QC, Canada/ NeuroRx Research Inc., Montreal, QC, Canada Dragana Obradovic, Department of Neurology, Military Medical Academy, Belgrade, Serbia Mark S Freedman, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada Mark Gudesblatt, South Shore Neurologic Associates, Patchogue, NY, USA Tjalf Ziemssen, Center of Clinical Neuroscience, Carl Gustav Carus University Hospital, Dresden, Germany Boris Kandinov, Ilda Bidollari, Maria Lopez-Bresnahan, Narinder Nangia*, David Rezendes, Richard Leigh-Pemberton Alkermes Inc, Waltham, MA, USA Lili Yang, Hailu Chen, Shifang Liu, Catherine Miller Biogen, Cambridge, MA, USA Jerome Hanna, Biogen, Maidenhead, UK * Employee of Alkermes Inc. at the time of the study and manuscript preparation Abstract Background: Diroximel fumarate (DRF) is a novel oral fumarate for patients with relapsing–remitting multiple sclerosis (RRMS). DRF and the approved drug dimethyl fumarate yield bioequivalent exposure to the active metabolite monomethyl fumarate; thus, efficacy/safety profiles are expected to be similar. However, DRF’s distinct chemical structure may result in a differentiated gastrointestinal (GI) tolerability profile. Objective: To report interim safety/efficacy findings from patients in the ongoing EVOLVE-MS-1 study. Methods: EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing DRF safety, tolerability, and efficacy in RRMS patients. Primary endpoint is safety and tolerability; efficacy endpoints are exploratory. Results: As of March 2018, 696 patients were enrolled; median exposure was 59.9 (range: 0.1–98.9) weeks. Adverse events (AEs) occurred in 84.6% (589/696) of patients; the majority were mild (31.2%; 217/696) or moderate (46.8%; 326/696) in severity. Overall treatment discontinuation was 14.9%; 6.3% due to AEs and <1% due to GI AEs. At Week 48, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (77%; p < 0.0001) and adjusted annualized relapse rate was low (0.16; 95% confidence interval: 0.13–0.20). Conclusion: Interim data from EVOLVE-MS-1 suggest DRF is a well-tolerated treatment with a favorable safety/efficacy profile for patients with RRMS. Keywords: Relapsing–remitting multiple sclerosis, multiple sclerosis, diroximel fumarate, monomethyl fumarate, clinical trial, disease-modifying therapy, safety, efficacy Date received: 6 May 2019; revised: 6 September 2019; accepted: 17 September 2019. View full publication.