Delayed-release Dimethyl Fumarate Demonstrates Long-term, Sustained Efficacy in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis followed for at least Eight-Years (P6.382)

Objective: Demonstrate sustained efficacy in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients treated with delayed-release dimethyl fumarate (DMF) for ~8 years. Background: Long-term follow-up data are useful to characterize the efficacy and safety of disease-modifying therapies when initiating treatment in newly diagnosed RRMS patients. DMF demonstrated strong efficacy and a favorable benefit-risk profile in RRMS patients in Phase 3 studies (DEFINE/CONFIRM), which is sustained in the associated ongoing extension study, ENDORSE (NCT00835770). Design/Methods: “Newly diagnosed” patients were diagnosed with MS ≤1 year before parent study entry and were either treatment-naive or previously treated with corticosteroids alone. In an integrated analysis of newly diagnosed patients from DEFINE, CONFIRM, and ENDORSE, annualized relapse rate (ARR) and expanded disability status scale (EDSS) score were assessed. Results are reported for patients treated with DMF 240 mg BID: placebo (PBO)/DMF (PBO for Years 0–2/DMF for Years 3–8) or continuous (DMF/DMF) treatment. Results: As of October 2016, 55% (79/144) DMF/DMF and 48% (41/85) PBO/DMF newly diagnosed patients remained on treatment; total follow-up (including DEFINE/CONFIRM) ~8 years (median 7.6 years, range 2.2–9.8). Over 8 years, adjusted ARR (95% CI) was 0.14 (0.10–0.18) for DMF/DMF and 0.16 (0.11–0.23) for PBO/DMF. For PBO/DMF, adjusted ARR (95% CI) was 0.25 (0.18–0.36) for Years 0–2 (PBO) and 0.09 (0.06–0.14) for Years 3–8 (DMF); the rate ratio (95% CI) was 0.37 (0.25–0.56; P Conclusions: ARR decreased significantly in PBO/DMF patients after initiating DMF, and remained low for newly diagnosed patients after 8 years. The proportion of patients with EDSS ≤3.5 remained stable over 8 years. Study Supported by: Biogen Disclosure: Dr. Gold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Diseases, Experimental Neurology and the Journal of Neuroimmunology. Dr. Gold has received research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis. Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Abbvie, Almirall, Atara Bio, Biogen, Sanofi-Genzyme, Genentech, GSK, Merck, Novartis. Dr. Giovannoni has received personal compensation in an editorial capacity for Elsevier as Editor of MSARDs. Dr. Giovannoni has received research support from Takeda. Dr. Phillips has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with consulting fees from Acorda, Biogen, Genentech, Genzyme, Merck Serono, Sanofi-Aventis, and Xenoport. Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for serving as consultant or speaker from Allozyne, Avanir, Biogen Idec, Novartis, Questcor, and Teva Pharmaceutical Industries. Dr. Fox has received research support from Biogen (clinical trial contracts) and Novartis (research study support). Dr. Yang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employee of and holds stock/stock options in Biogen. Dr. Yang holds stock and/or stock options in employee of and holds stock/stock options in Biogen, which sponsored research in which Dr. Yang was involved as an investigator. Dr. Yang holds stock and/or stock options in employee of and holds stock/stock options in Biogen. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with employee of and holds stock/stock options in Biogen. Dr. Miller holds stock and/or stock options in 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 employee of and holds stock/stock options in Biogen.