BG-12
- Overview
- How does it work?
- How is it given?
- What are the results so far?
- Side effects
- What further studies are planned?
- References
Overview
| Drug in development |  |
|---|---|
| BG-12 |  |
| Other names | BG00012, dimethyl fumarate, Panaclar |
| What is it for? | Relapsing remitting multiple sclerosis (MS) |
- 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
- The manufacturer has submitted BG-12 for licensing in Europe.
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 given?
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.
Results from two phase III trials were reported in 2011.
-
DEFINE - Efficacy and safety of oral BG00012 in relapsing-remitting multiple sclerosis
-
CONFIRM - Efficacy and safety study of oral BG00012 with active reference in relapsing-remitting multiple sclerosis
This phase III, 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.
Results of this study were presented at ECTRIMS/ACTRIMS 2011 held in Amsterdam 19-22 October, abstracts 95, P1071, P831, P994.
This phase III 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.
The manufacturer intends to present detailed data at a future scientific meeting.
Side effects
No serious side effects have been reported from clinical trials.
The most common side effects were:
- flushing and feeling hot
- gastrointestinal upset - diarrhoea, nausea, abdominal pain
- headache
What further studies are planned?
-
EXPLORE - Trial to evaluate oral BG-12 as combination therapy for patients who continue to experience disease progression despite ongoing treatment
-
Long-term safety and efficacy study of oral BG00012 monotherapy in relapsing-remitting multiple sclerosis
This phase II open-label study will evaluate the safety and tolerability of BG-12 when administered with beta interferons or glatiramer acetate to 100 people who continue to have evidence of disease activity despite receiving consistent monotherapy for at least a year. Efficacy endpoints will also be assessed in a subset of participants.
Estimated completion date June 2012.
Further details of this study.
An extension study for participants on the DEFINE and CONFIRM studies to assess the long-term effectiveness and safety of BG-12 for a further two years.
Estimated completion date June 2016.
Further details of this study.
References
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