Two New Pivotal Trials in MS

Hans-Christoph Diener, MD, PhD


November 15, 2012

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My name is Christoph Diener. I am a neurologist from Germany, and my topic today is multiple sclerosis. In the September 20 issue of the New England Journal of Medicine, 2 pivotal trials were published on a new drug for the treatment of relapsing multiple sclerosis: BG-12 (dimethyl fumarate), a substance that is approved for treatment of psoriasis. The drug has anti-inflammatory properties and also prevents destruction of astroglia and neurons.

In the first study (the DEFINE study),[1] 1200 patients with relapsing-remitting multiple sclerosis were randomly assigned to 3 groups. The first group received oral BG-12 240 mg twice daily. The second group took BG-12 three times daily, and the third group took a placebo. The primary endpoint was the relapse rate after 2 years.

This relapse rate was 27% for twice-daily BG-12, 26% for 3-times-daily BG-12, and 46% for placebo, which was highly significant. The drug also had a significant impact on the progression of disability of multiple sclerosis. The proportion of patients with confirmed progression of disability was 16% and 18%, for twice-daily and 3-times-daily BG-12, respectively, and 27% with placebo. BG-12 also resulted in fewer new gadolinium-enhancing lesions on MRI and new T2 lesions. Adverse events were mild, usually flushing or gastrointestinal side effects, and some patients had an increase in liver enzymes.

The second study, which was done simultaneously, is the CONFIRM study.[2] This study, which had 1417 patients, had 4 arms; 2 arms with oral BG-12 twice daily or 3 times daily; a placebo group; and a comparator group that received glatiramer acetate, which needs to be injected subcutaneously on a daily basis. After 2 years, the reduction in relapse rate was 44% with BG-12 twice daily, 51% with 3 times daily BG-12, and 29% for glatiramer acetate. The treatment had no effect on disease progression. T2 lesions and new gadolinium-enhancing lesions were also fewer in the active treatment group, but there was no difference between BG-12 and glatiramer acetate. Adverse events were similar to those found in the DEFINE study.

Taken together, this new oral medication is relatively well tolerated, with no severe side effects or no malignancies. This will be a very good alternative to the present medication. The drug is given orally and does not have to be injected subcutaneously or intramuscularly, and there are no serious life-threatening events, as are sometimes seen with the other new multiple sclerosis drugs. We have a new option for the treatment of relapsing-remitting multiple sclerosis, BG-12.

I am Christoph Diener, from the Department of Neurology at the University of Essen.