Objective: To evaluate clinical and radiological efficacy in relapsing-remitting multiple sclerosis (RRMS) patients who received diroximel fumarate (DRF) or dimethyl fumarate (DMF) in EVOLVE-MS-2 and continued DRF in EVOLVE-MS-1. Background: DRF is an investigational, oral fumarate for relapsing forms of MS. DMF is an approved treatment option for relapsing forms of MS. DRF and DMF produce bioequivalent exposure of the active metabolite, monomethyl fumarate, and are therefore expected to have similar efficacy and safety profiles. DMF has previously demonstrated significant reduction in risk of relapse at 2 years compared with placebo in RRMS patients; reductions were observed as early as Week 10. Design/Methods: EVOLVE-MS-2 (NCT03093324) is a randomized, double-blind, 5-week, phase 3 study evaluating gastrointestinal tolerability of DRF versus DMF in patients with RRMS. Patients who completed EVOLVE-MS-2 were eligible to roll over into EVOLVE-MS-1 (NCT02634307), an ongoing, open-label, phase 3 study evaluating DRF safety and exploratory efficacy over 96 weeks. Gd+ lesion counts were evaluated during the screening period before each study (~7 weeks apart), and again at Week 48 of EVOLVE-MS-1. A nonparametric signed rank test was used to determine if change in Gd+ lesion count between any 2 visits was significantly different from zero. EVOLVE-MS-2 patients remained blinded for treatment group as of this analysis. Results: Of the 289 patients who completed screening visits for both studies, 81 completed Week 48 to date in the ongoing EVOLVE-MS-1 study. Mean (SD) Gd+ lesion count was significantly reduced from screening in EVOLVE-MS-2 (1.1 [2.65]) to Week 48 in EVOLVE-MS-1 (0.2 [1.24]; 81.8% reduction; mean [SD] change: −0.9 [2.49], p Conclusions: DRF significantly reduced Gd+ lesions during the ~1-year treatment period. Significant reductions were observed as early as 7 weeks after initiating DRF and DMF treatment. Study Support: Biogen/Alkermes Disclosure: Dr. Singer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting and/or speaking fees from AbbVie, Acorda, Alexion, Bayer, Biogen, Celgene, EMD Serono, Genentech, Novartis, Roche, Sanofi Genzyme, Teva and TG Therapeutics. Dr. Singer has received research support from Barry Singer has received research grant support from AbbVie, Alkermes, Biogen, MedImmune, Novartis, Roche, and Sanofi Genzyme. Dr. Shafer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker/consulting fees from and advisory boards for Acorda, Biogen, Genentech, Mallinckrodt, Novartis, and Sanofi-Genzyme. Dr. Shafer has received research support from Research support from Acorda, Actelion, Adamas, Alkermes, Biogen, Boehringer Ingelheim, Chugai, Genentech, Lundbeck, Novartis, Opexa, Pfizer, Roche, Sanofi-Genzyme, and Sunovion. Dr. Arnold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant fees from Albert Charitable Trust, Biogen, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, MedDay, Merck Serono, Novartis, Sanofi-Aventis. Dr. Arnold holds stock and/or stock options in NeuroRx Research. Dr. Arnold has received research support from Research grants from Albert Charitable Trust, Biogen, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, MedDay, Merck Serono, Novartis, Sanofi-Aventis. Dr. Bowen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory, consultancy, and speaker activities for Alexion, Alkermes, Biogen, Celgene, EMD Serono, Genzyme, Genentech, Novartis, TG Therapeutics. Dr. Bowen holds stock and/or stock options in Holds stock in Amgen. Dr. Bowen has received research support from Research support from Alexion, Alkermes, Biogen IDEC, Celgene, Genzyme, Genentech, Novartis, TG Therapeutics. Compensation for consulting (Acorda Therapeutics, Bayer, Biogen, Cephalon, EMD Serono, Novartis, Pfizer, Questcor, Sanofi, Strativa, Teva, and UCB)Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Chen holds stock and/or stock options as a Full-time employee of Biogen and holds stock/stock options in Biogen which sponsored research in which Dr. Chen was involved as an investigator. Dr. Chen holds stock and/or stock options in options in Biogen. Dr. Hanna has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Hanna holds stock and/or stock options in Biogen which sponsored research in which Dr. Hanna was involved as an investigator. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Biogen. Dr. Miller holds stock and/or stock options in Full-time employee of and holds stock/stock options in Biogen which sponsored research in which Dr. Miller was involved as an investigator. Dr. Miller holds stock and/or stock options in Full-time employee of and holds stock/stock options in Biogen. Dr. Leigh-Pemberton has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Full-time employee of and holds stock/stock options in Alkermes. Dr. Leigh-Pemberton holds stock and/or stock options in Full-time employee of and holds stock/stock options in Alkermes which sponsored research in which Dr. Leigh-Pemberton was involved as an investigator. Dr. Leigh-Pemberton holds stock and/or stock options in Full-time employee of and holds stock/stock options in Alkermes.. Dr. Naismith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Alkermes, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, TG Therapeutics, Viela Bio. Dr. Naismith has received personal compensation in an editorial capacity for Associate Editor, NEJM Journal Watch.