Kate Dawson, MD, Senior Director, Medical Research, Biogen Idec, Cambridge, Mass.
Drug Discovery & Development - October 13, 2010
Multiple sclerosis (MS) is a chronic, progressive neurological disease that causes inflammation and demyelination in the central nervous system, often leading to declines in physical and mental function.
The most prevalent form of MS is relapsing-remitting MS (RRMS), which affects about 85% of MS patients and is characterized by unpredictable symptom exacerbations followed by periods of partial or complete recovery. Even with treatment, the disease can progress, resulting in more severe and frequent relapses and disability.
Biogen Idec’s BG-12 is an oral formulation of dimethyl fumarate. This is the first compound in clinical trials to activate the Nrf2 transcriptional pathway, a central mechanism of cellular defense against oxidative and metabolic stress.
This pathway has demonstrated both neuroprotective and anti-inflammatory properties. Clinical evidence suggests that BG-12 may provide this dual effect in treating MS by reducing inflammation caused by the disease and promoting neuroprotection, potentially preventing further cell damage and tissue loss that trigger common MS physical symptoms.
Current MS therapies often suppress or modulate the immune system, which can have negative effects on patients. By activating a cytoprotective mechanism, BG-12 may defend against the impact of MS. In addition, through completion of Phase 2 trials, there has been no evidence of BG-12 causing systemic immunosuppression.
In its Phase 2b monotherapy study, BG-12 reduced the mean number of new gadolinium enhancing (Gd+) lesions by 69% over weeks 12 through 24 in patients with RRMS compared to placebo. The presence of Gd+ lesions is thought to indicate inflammation within the nervous system. The safety and tolerability profile in this study supported development of BG-12 in further trials.1 BG-12 is currently being investigated as a treatment of RRMS as monotherapy in two Phase 3 clinical trials, DEFINE and CONFIRM, and in combination with interferons or glatiramer acetate in a Phase 2a trial, EXPLORE.
BG-12 received Fast Track designation from the U.S. Food and Drug Administration in 2008. Data from the ongoing trials are expected in 2011.
Reference
1. Kappos L, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet Neurology. 2008;372(9648):1463-1472.
The most prevalent form of MS is relapsing-remitting MS (RRMS), which affects about 85% of MS patients and is characterized by unpredictable symptom exacerbations followed by periods of partial or complete recovery. Even with treatment, the disease can progress, resulting in more severe and frequent relapses and disability.
Biogen Idec’s BG-12 is an oral formulation of dimethyl fumarate. This is the first compound in clinical trials to activate the Nrf2 transcriptional pathway, a central mechanism of cellular defense against oxidative and metabolic stress.
This pathway has demonstrated both neuroprotective and anti-inflammatory properties. Clinical evidence suggests that BG-12 may provide this dual effect in treating MS by reducing inflammation caused by the disease and promoting neuroprotection, potentially preventing further cell damage and tissue loss that trigger common MS physical symptoms.
Current MS therapies often suppress or modulate the immune system, which can have negative effects on patients. By activating a cytoprotective mechanism, BG-12 may defend against the impact of MS. In addition, through completion of Phase 2 trials, there has been no evidence of BG-12 causing systemic immunosuppression.
In its Phase 2b monotherapy study, BG-12 reduced the mean number of new gadolinium enhancing (Gd+) lesions by 69% over weeks 12 through 24 in patients with RRMS compared to placebo. The presence of Gd+ lesions is thought to indicate inflammation within the nervous system. The safety and tolerability profile in this study supported development of BG-12 in further trials.1 BG-12 is currently being investigated as a treatment of RRMS as monotherapy in two Phase 3 clinical trials, DEFINE and CONFIRM, and in combination with interferons or glatiramer acetate in a Phase 2a trial, EXPLORE.
BG-12 received Fast Track designation from the U.S. Food and Drug Administration in 2008. Data from the ongoing trials are expected in 2011.
Reference
1. Kappos L, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet Neurology. 2008;372(9648):1463-1472.
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