AMSTERDAM—Results from a large phase 3 trial support the potential of BG-12 (dimethyl fumarate) as an effective oral treatment for patients with relapsing-remitting MS. According to researchers, BG-12 may have dual anti-inflammatory and neuroprotective effects via the Nrf2 pathway.
DEFINE was a randomized, double-blind, placebo-controlled, multicenter trial that evaluated the efficacy and safety of BG-12 over two years in patients with relapsing-remitting MS. Patients ages 18 to 55 with relapsing-remitting MS and an EDSS score of 0 to 5 (inclusive) were randomly assigned to placebo, BG-12 240 mg BID, or BG-12 240 mg TID. All patients underwent clinical assessments at screening, baseline, and every four weeks for up to two years. The primary endpoint was proportion of patients relapsing at two years. Secondary efficacy endpoints at two years were annualized relapse rate and disability progression as measured by EDSS score.
A total of 1,234 patients were randomized; 408 received placebo, 410 received BG-12 BID, and 416 received BG-12 TID. According to findings presented at the ECTRIMS/ACTRIMS 5th Joint Triennial Congress, all primary and secondary endpoints were met. BG-12 BID and TID reduced the risk of relapse by 49% and 50%, respectively, compared with placebo at two years. Annualized relapse rate was 0.36 with placebo, and 0.17 and 0.19 with BG-12 BID and TID, corresponding to reductions of 53% and 48% for BG-12 BID and TID. The risk of confirmed 12-week disability progression was reduced by 38% for the BID dosing and by approximately 34% with TID dosing.
The overall incidence of adverse and serious adverse events was similar among the three groups.