Biogen Idec has announced new data from studies evaluating oral BG-12 (dimethyl fumarate), which provide further evidence supporting its strong clinical and radiological effects in people with relapsing-remitting multiple sclerosis (RRMS) and reinforce its favorable safety profile seen to date. These data were presented at the 28th Congress of the European Committee for the Treatment and Research of Multiple Sclerosis (ECTRIMS) in Lyon, France.
In a pre-specified analysis of integrated, or pooled, data from the phase III DEFINE and CONFIRM studies, dimethyl fumarate showed statistically significant and clinically relevant effects in reducing multiple sclerosis (MS) relapses and progression of disability, as well as reductions in magnetic resonance imaging (MRI) measures of disease activity. In addition, interim safety data from a phase III extension study indicate that continued exposure to dimethyl fumarate did not result in any new or worsening safety signals, and that its safety and tolerability profiles were consistent with previous studies.
“These data provide additional insight into the positive efficacy and safety results from our phase III studies, showing there is a consistent beneficial effect with dimethyl fumarate in reducing MS relapses, brain lesions and disability,” said Alfred Sandrock, MD, PhD., senior vice president, Development Sciences and chief medical officer of Biogen Idec. “If approved, dimethyl fumarate may provide a broad range of MS patients with an effective therapy that offers the ease of oral administration and an acceptable tolerability profile.”
DEFINE and CONFIRM were randomized, double-blind studies that compared the efficacy and safety of dimethyl fumarate 240 mg, administered twice daily (BID) or three times daily (TID), to placebo over two years. CONFIRM also included a reference comparator of glatiramer acetate (GA; 20 mg subcutaneous daily injection). A pooled analysis of the efficacy data from more than 2,300 patients in these two studies was performed in order to provide the medical community with a more precise estimate of dimethyl fumarate’s treatment effects versus placebo on relapse, progression and MRI outcomes.
“These pooled results demonstrate that dimethyl fumarate had a significant effect on measures that MS patients are acutely aware of – the frequency of the relapses they experience and the progression of disability,” said Ralf Gold, PhD, professor/chair of the Department of Neurology at St. Josef-Hospital/Ruhr-University in Bochum, Germany. “As a physician who treats patients with MS, the strong results observed in the phase III studies of dimethyl fumarate indicate that it may provide an attractive combination of efficacy, safety and tolerability.”
DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS) was a global, randomized, double-blind, placebo-controlled, dose-comparison study to determine the efficacy and safety of dimethyl fumarate (240 mg, BID or TID) and enrolled 1,237 people with RRMS. The primary objective was to determine if dimethyl fumarate was effective in reducing the proportion of relapsing patients at two years. Secondary endpoints included reduction in the number of new or newly enlarging T2-hyperintense lesions and Gd+ lesions as measured by MRI, reduction in ARR, and reduction of disability progression as measured by EDSS. Additional endpoints included the safety and tolerability of dimethyl fumarate.
CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS) was a global, randomized, double-blind, placebo-controlled, dose-comparison study to determine the efficacy and safety of dimethyl fumarate and enrolled 1,430 people with RRMS. The study evaluated two dose regimens of dimethyl fumarate, 240 mg BID and 240 mg TID, as well as a reference comparator of GA (20 mg subcutaneous daily injection). Both dimethyl fumarate and GA groups were evaluated versus placebo. The primary objective was to determine whether dimethyl fumarate was effective in reducing the rate of clinical relapses at two years. Secondary endpoints at two years included reduction in: the number of new or newly enlarging T2-hyperintense lesions and the number of new non-enhancing T1-hypointense lesions (MRI scans were obtained at a cohort of sites); the proportion of patients who relapsed; and in progression of disability as measured by EDSS. Safety and tolerability of dimethyl fumarate were also assessed.
ENDORSE is an ongoing global, dose-blind extension study to determine the long-term safety and efficacy of dimethyl fumarate (240 mg, BID or TID). The study has enrolled 1,738 patients with RRMS who completed the DEFINE study or the CONFIRM study. Patients participating in ENDORSE will be followed for up to five years. The primary objective is to evaluate the long-term safety profile of dimethyl fumarate. Secondary objectives include: long-term efficacy of dimethyl fumarate on clinical outcomes and MS brain lesions on MRI scans; and effects of dimethyl fumarate on quality of life measurements. It is estimated that the ENDORSE study will be completed in 2016.
Dimethyl fumarate, also known as BG-12, is an investigational oral therapy in late-stage clinical development for the treatment of RRMS, the most common form of MS. Dimethyl fumarate is the only currently known investigational compound for the treatment of RRMS that has experimentally demonstrated activation of the Nrf-2 pathway.
Dimethyl fumarate is currently under review by regulatory authorities in the United States, European Union, Australia, Canada and Switzerland.
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