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.