Latest research on BG-12

Dimethyl fumarate is an anti-inflammatory. It is indicated for multiple sclerosis patients with relapsing forms and is also being investigated for the treatment of psoriasis. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.

BG-12 dosage

The results showed that the estimated treatment effects of both BG-12 doses tested (240 mg two or three times daily) were equivalent to or better than those achieved with GA in terms of efficacy endpoints. [source, 2015]
In the second pivotal trial, the Comparator and an Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (CONFIRM) study, BG-12 at both dosages was tested against placebo or open-label active comparator glatiramer acetate41. [source, 2015]
In the subgroup undergoing MRI scan BG-12 also yielded a reduction of the number of new/newly enlarging lesions and gadolinium enhancing lesions by 80-92 per cent at both dosages. [source, 2015]
Two BG-12 dosage regimens were included in the analysis: 240 mg twice daily or 240 mg three times daily (on the basis of preclinical results), and the follow-up period should be adequately long in order to determinate the efficacy and safety outcomes accurately. [source, 2014]
In phase IIb RCT [38, 39] adult patients with RRMS were given BG-12 at a dose of 120 mg once daily, 120 mg three times daily or 240 mg three times daily or placebo during 24 weeks of treatment, followed by additional 24 weeks for dose-blinded safety assessment. [source, 2014]
We performed a meta-analysis of the results from DEFINE[15-19] and CONFIRM [20-24] trials that compared BG-12 separately for both dosages (240 mg twice daily or three times daily) with a placebo. [source, 2014]
Results concerning comparison between BG-12 at a dose of 240 mg three times daily and placebo from Kappos et al. study [38, 39] were excluded from the meta-analysis because the reported outcomes were extracted at week 24, whereas results in studies DEFINE [15-19]and CONFIRM [20-24] were obtained at 96 weeks of treatment period; therefore, they should not be aggregated together. [source, 2014]
Therefore, the overall result of the meta-analysis of BG-12 efficacy (at both dosages) revealed a statistically significant difference in the proportion of patients who had a relapse in favor of the BG-12 over the placebo (for BG-12 twice daily RRfixed=0.64 [95% CI: 0.56–0.74], p<0.00001; for BG-12 three times daily RRfixed=0.58 [95% CI: 0.50–0.67], p<0.00001) (Fig. [source, 2014]
However, the result of comparison between lower dosage of BG-12 (240 mg twice daily) and GA showed no statistically significant differences between groups (RR=0.91 [95% CI: 0.72–1.13], p>0.05). [source, 2014]
In study [38, 39], there was no statistically significant difference between BG-12 at a dose of 240 mg three times daily and placebo in respect to the relative risk of relapse during 24 weeks of treatment (RR=0.77 [95% CI: 0.40–1.48], p>0.05). [source, 2014]