Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study

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.