Two large Phase III studies for the oral medication BG-12 (dimethyl fumarate) have demonstrated significant and clinically meaningful reductions in relapses and brain lesions in people with relapsing-remitting MS (RRMS) compared with placebo. The studies, reported in The New England Journal of Medicine, also showed a benefit in slowing disease progression.
In the new studies, called Define and Confirm, participants were randomized into two groups, taking 240 milligrams of BG-12 either twice or three times a day. Those in a third group took a placebo. The combined results showed that the drug reduced the relapse rate by about 50 percent. There was minimal difference between the two-times-a-day and three-times-a-day regimens.
Taking BG-12 twice a day reduced the number of new or newly enlarging brain lesions by 71 percent to 99 percent, depending on the type of lesion and the study. The Define study found a statistically significant 38 percent reduction in the progression to disability.
The most frequent side effects were a temporary flushing and warm feeling and gastrointestinal symptoms including nausea, diarrhea, cramping and vomiting. Though both types of side effects were common, they tended to diminish after the first few weeks of use and were tolerated by most participants.
BG-12, which is being developed by Biogen Idec, is an anti-inflammatory that works by protecting nerves against injury. It is a fumaric acid, very similar to one widely used in Germanyfor the treatment of psoriasis. Researchers are hoping that the U.S. Food and Drug Administration will make a decision on the new drug application for BG-12 by the end of the year.
“BG-12 represents a potentially exciting addition to the toolbox of MS therapies. The DEFINE and CONFIRM trials have shown this drug to be safe and effective in people with relapsing-remitting MS,” says Ben Thrower, M.D., Senior Medical Advisor for the Multiple Sclerosis Foundation. “So, where will we use BG12? I see BG12 as a first-line therapy to be considered in people who are newly diagnosed or who are struggling with an injectible MS therapy due to side effects. If a person is doing well with their current injectible therapy, we will need to consider the risks and benefits of switching to BG12.”
Dr. Thrower adds, “A more challenging group will be those looking at switching from Tysabri to BG12. Very few study subjects in the CONFIRM and DEFINE trials were moving from Tysabri to BG12, so we have very little data to rely on. For people who are JC virus antibody positive, we will need to look at the risks and benefits of staying on Tysabri versus switching to BG12. To sum it all up, I'm excited about BG12 and think it may be a good fit for many of our patients.”