DX66
Long-Term Follow-up of the Safety of Delayed-Release Dimethyl Fumarate in Relapsing-Remitting Multiple Sclerosis: Interim Results from the ENDORSE Extension Study

Friday, May 29, 2015
Griffin Hall
J. Theodore Phillips, MD, PhD, FAAN , Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX
Robert J. Fox, MD, FAAN , Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH
Krzysztof W Selmaj, MD, PhD , Department of Neurology, Medical Academy of Lodz, Lodz, Poland
Carlo Pozzilli, MD , University of Rome, Rome, Italy
Ray Zhang, PhD , Biogen Idec, Inc., Cambridge, MA
Mark Novas, MD , Biogen Idec, Inc., Cambridge, MA
Marianne T. Sweetser, MD, PhD , Biogen Idec, Inc., Cambridge, MA
Ralf Gold, MD , St Josef Hospital, Ruhr University Bochum, Bochum, Germany



Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated broad efficacy and an acceptable safety profile in the Phase 3 DEFINE and CONFIRM studies. ENDORSE is an 8-year extension of DEFINE and CONFIRM.

Objectives: To report safety outcomes from ENDORSE, investigating long-term effects of DMF in patients with relapsing-remitting multiple sclerosis.

Methods: Patients randomized to DMF 240 mg twice (BID) or three times daily (TID) in DEFINE or CONFIRM continued on the same dosage in ENDORSE. Patients randomized to placebo (PBO; DEFINE/CONFIRM) or glatiramer acetate (GA; CONFIRM) were re­-randomized 1:1 to DMF 240 mg BID or TID. Adverse events (AEs) were analyzed according to treatment received in the parent/extension study: BID/BID (n=501), TID/TID (n=501), PBO/BID (n=249), PBO/TID (n=248), GA/BID (n=118), and GA/TID (n=119).

Results: As of May 14, 2014, total follow-up in ENDORSE for all groups was 4,981 patient-years. Overall incidence of AEs was as follows: BID/BID, 91%; TID/TID, 92%; PBO/BID, 95%; PBO/TID, 93%; GA/BID, 88%; and GA/TID, 85%. Multiple sclerosis (MS) relapse and nasopharyngitis were the most common AEs in patients continuing DMF; MS relapse and flushing were most common in those new to DMF. Flushing and gastrointestinal-related events were more common among patients new to DMF. Incidence of serious AEs (SAEs) was: BID/BID, 22%; TID/TID, 25%; PBO/BID, 24%; PBO/TID, 16%; GA/BID, 16%; and GA/TID, 19%. The most common SAE was MS relapse; other individual SAEs occurred in no more than five patients in any treatment arm. Incidence of AEs leading to discontinuation was 6% to 7% and 14% to 26% in patients continuing and new to DMF, respectively. Incidence of serious infections was ≤4% in all groups, with no confirmed opportunistic infections.* There were no new findings in hematologic outcomes compared with DEFINE and CONFIRM. Hepatic AEs occurred in ≤3% of patients in any group; there was no evidence of increased risk of renal or urinary events. There were 27 malignancies in 26 patients (18 continuing treatment and 8 new to DMF). There were five deaths, none of which was considered related to study drug.

Conclusions: Sustained treatment with DMF continues to demonstrate a favorable benefit: risk profile.

*Note: after the May 2014 data cut, a case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia (approximately <0.5x109/L of 3.5 years duration).

Study supported by: Biogen Idec

See more of: Disease Management, Mechanisms, and Treatment (Poster)
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