DX29
Safety Profile of Delayed-Release Dimethyl Fumarate in Relapsing-Remitting MS: Long-Term Interim Results from the ENDORSE Extension Study

Thursday, May 29, 2014
Trinity Exhibit 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 Selmaj, MD, PhD , Department of Neurology, Medical University of Lodz, Lodz, Poland
Ray Zhang, PhD , Biogen Idec, Inc., Cambridge, MA
Mark Novas, MD , Biogen Idec, Inc., Cambridge, MA
Marianne Sweetser, MD, PhD , Biogen Idec, Inc., Cambridge, MA
Vissia Viglietta, MD, PhD , Biogen Idec, Inc., Cambridge, MA
Ralf Gold, MD , Department of Neurology, St Josef Hospital, Ruhr University, Bochum, Germany
PDF


Background: Delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and an acceptable safety profile in patients with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. ENDORSE is an ongoing, 5-year, dose-blind extension of DEFINE and CONFIRM.

Objectives: To report long-term interim safety results from ENDORSE.

Methods: Patients randomized to delayed-release DMF 240 mg twice (BID) or three times daily (TID) in DEFINE/CONFIRM continued the same dosing regimen in ENDORSE. Placebo (PBO; DEFINE/CONFIRM) and glatiramer acetate (GA; CONFIRM) patients were randomized 1:1 to delayed-release DMF BID or TID. Safety data were analyzed according to parent/extension study treatment: BID/BID, TID/TID, PBO/BID, PBO/TID, GA/BID, GA/TID.

Results: As of 12 June 2013 data cut, the overall incidences of adverse events (AEs) were: 89% BID/BID (n=501), 90% TID/TID (n=501), 93% PBO/BID (n=249), 90% PBO/TID (n=248), 86% GA/BID (n=118), 84% GA/TID (n=119). The incidences of serious AEs were: 18% BID/BID, 19% TID/TID, 22% PBO/BID, 15% PBO/TID, 13% GA/BID, 18% GA/TID. The incidence of discontinuations due to AEs was 4%–6% (BID/BID, TID/TID) and 14%–23% (PBO/BID, PBO/TID, GA/BID, GA/TID). The incidence of serious infections was ≤3% (all groups). There were no confirmed opportunistic infections and no new findings in hematologic outcomes compared with DEFINE/CONFIRM. Hepatic AEs occurred in ≤3% of patients in any treatment group. There was no evidence of increased risk of renal or urinary events. There were 20 malignancies in 19 patients (11 continuing and 8 new to delayed-release DMF). There were 4 deaths, none of which was considered related to study drug.

Conclusions: The long-term safety profile of delayed-release DMF appears consistent with findings from DEFINE/CONFIRM. No new or worsening safety signals were observed.

See more of: Disease Management, Mechanisms, and Treatment (Poster)
See more of: CMSC
<< Previous Abstract | Next Abstract >>