BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. RESULTS: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. CONCLUSION: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.

Baylor Institute for Immunology Research Multiple Sclerosis Program Dallas TX USA

Biogen Cambridge MA USA

Cleveland Clinic Mellen Center for Multiple Sclerosis Treatment and Research Cleveland OH USA

Department of Neurology 1st Faculty of Medicine Charles University Prague Prague Czech Republic

Department of Neurology and Psychiatry Sapienza University of Rome Rome Italy

Department of Neurology St Josef Hospital Ruhr University Bochum Bochum Germany

Department of Neurology University Hospital of Basel Basel Switzerland

Medical University of Lodz Lodz Poland

Montreal Neurological Institute McGill University Montreal QC Canada

NeuroRx Research Montreal QC Canada Montreal Neurological Institute McGill University Montreal QC Canada

NMR Research Unit Queen Square Multiple Sclerosis Centre University College London Institute of Neurology London UK

St Vincent's University Hospital Dublin Ireland

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