BG-12 for the Treatment of Relapsing-Remitting Multiple Sclerosis, United States of America

BG-12 (Dimethyl fumarate) is an investigational drug indicated for treating relapsing-remitting multiple sclerosis (RRMS). The drug was developed by Biogen Idec.

The drug received fast-track designation from the US Food and Drug Administration (FDA) in 2008.

Biogen reported positive results from the first of two phase III clinical trials in April 2011. The company plans to file a new drug application (NDA) after getting results from the second phase III clinical trials in 2012.

Relapsing / remitting multiple sclerosis (RRMS)

Multiple sclerosis (MS) is a chronic disease caused when the myelin insulation that covers the nerve fibres (neurons) in the central nervous system gets damaged.

Sensation, movement and bodily functions are affected in MS patients. The disease has four internationally recognised forms and RRMS is one.

The US National MS Society estimated that more than 2.5 million people in the world and 400,000 people in the US alone are affected by MS. It is estimated that 85% of the people diagnosed with MS have the RRMS form of the illness.

BG-12 mechanism of action

BG-12 drug belongs to a fumaric acid esters class. The drug is under investigation for the treatment of RRMS. The mechanism of action of the drug is not understood completely, however, clinical trials on BG-12 suggest that the drug works by suppressing the inflammatory response and provides protection against nerve cell death. The drug prevents attack on CNS by the immune system and it also protects neurons from the attack.

Clinical trials 

Biogen conducted phase I clinical trials on BG-12 between February and October 2009. The study enrolled 48 patients with RRMS in study centres across Germany and the UK. The study results established the pharmacokinetic (PK) profile of BG-12.

The company initiated open-label and multicentre phase II clinical trials (EXPLORE study) on BG-12 in May 2010. The results of the study are expected to be out in October 2011. The study enrolled 100 patients across 21 study centres in the US.

The primary outcome measure of the study will be to evaluate the safety and tolerability of BG-12. The secondary outcome measure will include exploring the efficacy of BG-12 in combination with IFNß or GA.

Biogen initiated a randomised, double-blind, placebo-controlled and multicentre first phase III clinical trial on BG-12 known as Define (determination of the efficacy and safety of oral fumarate in relapsing-remitting MS) study. The study was conducted between January 2007 and February 2011. The study was conducted on more than 1,200 patients across 169 study locations in the world. The patients were administered with a 240mg dose of BG-12 two or three times a day.

The Define study results were announced in April 2011. The results showed that BG-12 met both primary and secondary endpoints of the study. BG-12 demonstrated a statistically significant reduction in the RRMS patients who relapsed at two years compared to placebo. The study results also showed a favourable safety and tolerability profile of BG-12.

Biogen initiated the second phase III clinical trials CONFIRM on BG-12 in June 2007. It is a randomised, placebo-controlled, active reference and multicenre study. The study enrolled 1,232 patients with RRMS across 206 international study locations.

The study will test the drug in comparison with a placebo and Copaxone (glatiramer acetate), which is an active comparator produced by Teva Pharmaceuticals.

The primary outcome measure of the study is to determine whether BG-12 when compared to placebo is effective in reducing the relapses inside a period of two years. The secondary outcome measure will include finding the safety and tolerability of BG-12 and also finding whether the drug decreases the brain lesions and slows down the progression. The results of the study are expected to come by September 2011.