Top-Line Results Positive for Oral BG-12 in RRMS

Megan Brooks

April 12, 2011

April 12, 2011 — Phase 3 results with oral BG-12 (dimethyl fumarate; Biogen Idec) in relapsing-remitting multiple sclerosis (RRMS) show significant clinical responses and favorable safety and tolerability, the company announced Monday.

The DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS) trial was a global, randomized, double-blind, placebo-controlled, dose-comparison study to determine the efficacy and safety of oral BG-12 in more than 1200 people with RRMS.

Top-line results show that 240 mg of BG-12, administered either twice or 3 times daily, met the primary study endpoint, demonstrating a highly statistically significant reduction (P < .0001) in the proportion of patients with RRMS who relapsed at 2 years compared with placebo.

Both doses of BG-12 also met all of the secondary study endpoints, providing a statistically significant reduction in the annualized relapse rate, in the number of new or newly enlarging T2 hyperintense lesions, and in new gadolinium-enhancing lesions as measured by magnetic resonance imaging, as well as in the rate of disability progression as measured by the Expanded Disability Severity Scale at 2 years.

The overall incidence of adverse events and serious adverse events was similar among the placebo group and both BG-12 treatment groups. The safety profile was consistent with what was seen in the phase 2 study of BG-12, the company notes.

These findings "represent an important step forward" in the development of BG-12 for MS, Douglas Williams, PhD, Biogen Idec's executive vice president of research and development, noted in a statement. "We are very pleased with these data and believe that BG-12 has the potential to offer MS patients a highly effective oral treatment option with a strong safety profile," he added.

Further analyses of the DEFINE study are ongoing, and the company anticipates presenting detailed data at a future medical meeting.

From Psoriasis to Multiple Sclerosis

BG-12 received fast track designation from the US Food and Drug Administration in 2008. It was initially developed as a treatment for psoriasis, first as a topical ointment and later as an oral drug. In psoriasis studies, reports began to surface that people with both MS and psoriasis were seeing improvement in their MS symptoms with treatment.

Subsequent mechanistic studies showed that the drug has immunomodulatory properties, including inhibiting expression of cytokines and adhesion molecules. The drug also seems to activate the Nrf2 transcriptional pathway, which has neuroprotective effects, including protection of the blood brain barrier and maintenance of myelin integrity.

In addition to DEFINE, another phase 3 clinical trial of BG-12 in RRMS, CONFIRM, is currently under way. This study compares BG-12 and an active comparator, glatiramer acetate, against placebo on clinical relapse, MRI measures of MS, progression of disability, and safety. Results from CONFIRM are expected in the second half of 2011.

The DEFINE study was funded by Biogen Idec.


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