BG-12 |
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Other names |
Tecfidera, dimethyl fumarate |
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What is it for? |
Relapsing remitting multiple sclerosis (MS) |
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- BG-12 is an experimental drug treatment for relapsing remitting multiple sclerosis. It is given as a tablet, two or three times daily.
- BG-12 may reduce the activity and impact of inflammatory cells in the central nervous system and have neuroprotective effects.
- In phase III studies, BG-12 reduced annual relapse rates by about 50% compared to placebo.
- Few serious side effects have occurred in clinical trials. The most common side effects have been:
- flushing and feeling hot
- gastrointestinal upset - diarrhoea, nausea, abdominal pain
- headache
- On 21 March 2013, CHMP (Committee for Medicinal Products for Human Use), part of the European Medicines Agency,recommended that BG-12 should be granted a license for treatment of adults with relapsing remitting multiple sclerosis. NICE has begun preliminary work on the appraisal with a decision expected in January 2014.
How does it work?
The mechanism of action is not fully understood, but preclinical studies have suggested that BG-12 may have complex neuroprotective and anti-inflammatory effects, acting via the Nrf-2 pathway. Activation of the Nrf-2 pathway defends against oxidative-stress induced neuronal death, protects the blood-brain barrier and supports maintenance of myelin integrity in the central nervous system.
How is it taken?
BG-12 is taken orally as tablets, two or three times per day.
What are the results so far?
In a phase II study, different doses of BG-12 were compared to placebo in people with relapsing remitting MS over 24 weeks of treatment. BG-12 significantly reduced MRI-detectable brain lesion activity. A 32% reduction in relapse rate was also observed but could not be considered significant since this measure was not included in the study design.
Two phase III trials found BG-12 effective at reducing the number of relapses to approximately half of that seen inthose taking placebo. In one study (DEFINE) the progression of disability was reduced for people taking BG-12; this effect was not seen in the second study (CONFIRM).
DEFINE - BG-12 compared to placebo
This 2 year study compared BG-12 taken either two or three times daily and placebo in more than 1200 participants with relapsing remitting MS. Compared to placebo, the drug reduced the annual relapse rate by 53% for the twice daily dosing and 48% for the three times a day dosing.
BG-12 twice daily reduced the risk of disability progression by 38% while BG-12 three times per day reduced this risk by 34%.
MRI scans showed that, after two years, people receiving BG-12 had significantly fewer brain lesions compared to placebo.
CONFIRM - BG-12 or glatiramer acetate compared to placebo
This two year study with 1232 participants was similar to DEFINE, but with an additional group who took glatiramer acetate (Copaxone) for comparison.
BG-12 reduced annual relapse rate by 44% for the twice-daily dose and by 51% for the three times daily dose, compared to placebo. In contrast, glatiramer acetate reduced relapse rate by 29%.
BG-12 twice daily reduced the risk of disease progression by 21% and for three times daily by 24%. These results were not statistically significant.
Side effects
The most common side effects were:
- flushing and feeling hot
- gastrointestinal upset - diarrhoea, nausea, abdominal pain
- headache
What further studies are planned?
No further clinical trials are currently underway.
References
Fox RJ, et al.
Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis
New England Journal of Medicine 2012 367:1087-1097
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Gold R, et al.
Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.
New England Journal of Medicine 2012 367:1098-1107
Read abstract
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 2008;372:1463-1472.
Read abstract
Kappos L, et al.
Effect of BG-12 on contrast-enhancing lesions in patients with relapsing-remitting multiple sclerosis: subgroup analyses from the phase 2b study.
Multiple Sclerosis 2011 Aug 30. [Epub ahead of print]
Read abstract
MacManus DG, et al.
BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis.
J Neurol. 2011 Mar;258(3):449-56.
Read abstract