Results Published: Oral Drug BG00012 Reduced MRI Inflammation in Relapsing-Remitting MS During Phase 2 Trial -- Phase 3 Trials Recruiting Patients

Results of a multicenter, controlled clinical trial of oral BG00012 (dimethyl fumarate, Biogen Idec, Inc) involving 257 people withrelapsing-remitting MShave now been published, showing that, compared to inactive placebo, the highest tested dose led to a 69% reduction in active inflammation on MRI scans from weeks 12 to 24. Adverse events included abdominal pain, flushing, headache, fatigue, and feeling hot. The study was conducted by Dr. Ludwig Kappos and colleagues, and results are published in the October 25, 2008 issue of The Lancet (2008 372:1463-1472). Based on these positive results, the sponsor is recruiting people with relapsing-remitting MS for two large-scale, Phase 3 clinical trials.

Background and Study Design

Multiple sclerosis occurs when the immune system mistakenly attacks nerve fiber-insulating myelin and other brain and spinal cord tissues. Although its exact mechanism of action is not known, BG00012, an oral fumarate, is thought to inhibit immune cells and molecules and may be protective against damage to the central nervous system.

For this Phase 2 study, 257 people with relapsing-remitting MS were assigned to receive a low dose, medium dose or high dose of daily oral BG0012, or inactive placebo, for 24 weeks. Participants were aged 18-55, with no to moderate disability (EDSS scores ranging from 0 to 5), and had had at least one relapse within one year of the study or MRI scans showing active disease.

The study was designed with a primary outcome to be a comparison of the total number of new, active brain lesions (as seen on MRI scans using gadolinium, an enhancing agent) at four-week intervals starting with week 12. The investigators also collected data on other MRI findings, relapse rates, and safety.

Results

Compared with those on placebo, the treatment group on the highest dose of BG00012 had a 69% reduction in the mean total number of new enhancing MRI lesions from weeks 12 to 24. The drug also reduced the number of other types of new or enlarging MRI lesions. No significant difference was seen in relapse rates, but the study was not designed to adequately detect clinical differences.

Based on the anti-inflammatory effects seen on MRI, the sponsor is proceeding with two large-scale, Phase 3 clinical trials of BG00012 in relapsing-remitting MS. Participants are being sought for the two trials, known as the DEFINE study and the CONFIRM study.Learn more about the possibility of participating in one of these clinical trials

Comment

“We are encouraged by the MRI data from this publication,” says Patricia O’Looney, PhD, Vice President of Biomedical Research for the National MS Society. “We look forward to seeing further clinical and safety data from the phase 3 studies, which will help to determine if this oral therapy can be used safely and effectively in people with MS.”