Kappos L et al. (2008) Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 372: 1463–1472

A placebo-controlled, dose-finding, phase II trial testing the efficacy and safety of BG00012, an oral formulation of dimethyl fumarate, reports a reduced incidence of gadolinium-enhancing lesions—indicative of inflammatory activity in the CNS—in patients with relapsing–remitting multiple sclerosis (MS).

Kappos et al. recruited 257 patients with relapsing–remitting MS (aged 18–55 years) from 43 medical centers in Europe and Russia. For the first 24 weeks, patients were randomly assigned to receive BG00012 120 mg once daily (n = 64), 120 mg three times daily (n = 64), or 240 mg three times daily (n = 64), or placebo (n = 65). In a 24-week extension period for safety assessment, patients receiving BG00012 continued on their assigned dose and the placebo group switched to the highest fumarate dose.

Compared with placebo, treatment with the highest BG00012 dose led to a 69% reduction in the mean number of new gadolinium-enhancing lesions on brain MRI scans from weeks 12 to 24, and reductions in T1-hypointense lesions and T2-hyperintense lesions of 53% and 48%, respectively. High-dose BG00012 also reduced the annualized relapse rate by 32%. No significant differences were observed between the lower-dose-BG00012 and placebo groups. Safety and tolerability profiles were similar in all treatment groups.

Kappos et al. suggest that BG00012 has immunomodulating effects and may also activate a pathway that protects against the oxidative stress implicated in the pathology of MS. Phase III trials are underway, which are anticipated to confirm the results of this study.