Key study points:
1. In patients with relapsing-remitting multiple sclerosis, twice-daily and thrice-daily BG-12 significantly reduced relapse rates and improved radiologic outcomes.
2. The study findings of BG-12 efficacy and safety profile generally agree with the concurrently published DEFINE trial by Gold et al (within same issue of NEJM).
Primer: Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system affecting 2.5 million people worldwide. It is commonly treated with parenteral agents such as interferon-beta and glatiramer acetate. BG-12 represents an oral formulation of dimethyl fumarate which is known to have anti-inflammatory and cytoprotective properties shown to be effective in patients with relapsing-remitting MS in prior phase II studies.
This [phase 3, randomized controlled] study: 1,430 patients with relapsing-remitting MS who were enrolled from 200 sites in 28 countries (1,417 in the intention-to-treat analysis) were included. They were randomly assigned in a 1:1:1:1 ratio to receive oral placebo, BG-12 at a dose of 240mg twice a day, BG-12 at a dose of 340mg thrice a day, or subcutaneous daily injections of 20mg of glatiramer acetate for 96 weeks. Patients and research personnel were blinded to assignment of oral treatment groups. The primary efficacy end point was the annualized relapse rate at 2 years. The annualized relapse rate was significantly lower with twice-daily BG-12 (0.22, p<0.001), three times daily BG-12 (0.20, p<0.001), and glatiramer acetate (0.29, p=0.01) compared to placebo (0.40). Looking at radiological end points, BG-12 and glatiramer acetate significantly reduced the mean number of new or enlarging hyperintense lesions on T2-weighted imaging and hypointense lesions on T1-weighted imaging, relative to placebo (p<0.001 for all comparisons). BG-12 and glatiramer acetate significantly reduced rate of relapse, though disability progression was not significantly reduced relative to placebo in this trial. The incidence of serious adverse events was similar across groups.
In sum: The above-described CONFIRM trial demonstrates that BG-12 (240mg, twice or thrice daily) significantly reduces rate of relapse in relapse-remitting MS patients. The efficacy findings are similar to those found by the phase 3 DEFINE trial, published in the same issue of NEJM (Gold et al 2012). Although this study was not designed to compare BG-12 versus glatiramer acetate, post-hoc analyses reveal greater treatment effect with thrice-daily BG-12 relative to glatiramer acetate but further studies should examine this further, as well as examining long-term usage efficacy and safety of BG-12. Regardless, this trial supports the use of oral BG-12 as an initial or alternate treatment option for patients with relapsing-remitting MS.
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