Preparations and administration: BG-12 (Tecfidera®) was approved in March 2013 for the treatment of patients with RRMS by the US regulatory Food and Drug Administration (FDA) and received a positive CHMP opinion from the European Medicines Agency (EMA). BG-12 is administered

orally at a dose of 240 mg twice daily. Clinical trials: a Phase III trial (determination of the efficacy and safety of oral fumarate in RRMS − DEFINE) with more than 1200 patients with RRMS compared BG-12 (2 × 240 mg/day or 3 × 240 mg/day for 96 weeks) to placebo [52]. BG-12 reduced the annualized relapse rate by about 53% from 0·36 to 0·17 (twice daily, P < 0·0001) and 48% from 0·36 to 0·19 (thrice daily, P < 0·0001). The proportion of patients with confirmed disability progression was lowered from 27% (placebo) to 16% (twice daily, P = 0·005) and 18% (thrice daily, P = 0·013). BG-12 at both dosages was also superior to placebo Bioactive Compound Library clinical trial Ponatinib ic50 with regard to various MRI parameters. Another Phase III trial (comparator and an oral fumarate in RRMS – CONFIRM) with more than 1200 patients with RRMS compared

BG-12 (2 × 240 mg/day or 3 × 240 mg/day for 96 weeks) to GA (20 mg/day s.c.) and placebo [53]. Importantly, the study was not powered to detect a difference between BG-12 and GA. BG-12 reduced the annualized relapse rate by 44% (0·22, twice daily, P < 0·001) and 51% (0·20, thrice daily, P < 0·001), whereas GA caused a reduction of 29% (0·29, P = 0·01) compared to placebo (0·40). BG-12 reduced the proportion of patients with confirmed Morin Hydrate disability progression by 21% (twice daily) and 24% (thrice daily), whereas GA caused a reduction of 7% compared to placebo. However, the latter results did not reach statistical significance in a preliminary analysis, due possibly to a very low disability

progression within the control group. BG-12 was also superior to placebo with regard to various MRI parameters. Participants from these two Phase III clinical trials may have continued into the ongoing extension phase (long-term safety and efficacy study of oral BG00012 monotherapy in relapsing−remitting MS – ENDORSE). To the best of our knowledge, clinical trials with BG-12 have not yet been performed in patients with CIDP or its variants. Adverse effects: in both Phase III clinical trials flush, diarrhoea, nausea, vomiting and abdominal pain as well as lymphopenia occurred more frequently with BG-12 compared with placebo; severe infections or deaths were not more common with BG-12 treatment compared to placebo. However, during the extension phase of both clinical trials, there were 14 malignancies in 13 patients – six in patients who continued on BG-12 and eight in patients who switched from placebo to BG-12. There were three deaths, none of which were considered related to the study drug [54].