Multiple sclerosis: Oral BG12 for treatment of relapsing-remitting MS

This review article looks at two large phase III trials which looked at the clinical efficacy and safety profile of oral dimethyl fumarate (BG12) in patients with relapsing remitting MS. The DEFINE study was a three-arm trial over 96 weeks evaluating BG-12 in two dosages (480mg and 720mg) versus placebo. The proportion of patients with a relapse within two years was 2%, 26% and 46% respectively. The annual relapse rate reduction was 53% and 48% for the lower and higher dosages of BG12. The relative risk reduction for disease progression compared with placebo was 48% in the 480mg BG12 group and 34% in the 720mg BG12 group. Also, the MRI parameters showed significant improvement. The CONFIRM study was a similar trial design, but with an additional, open fourth arm to compare daily subcutaneous injections of 20mg glatiramer acetate. The annual relapse rate reductions relative to placebo was 44%, 51% and 29% for 480mg BG12, 720mg BG12 or glatiramer acetate respectively. The reduction of disease progression was not significant for BG12 or glatiramer acetate. MRI parameters were markedly changed in patients who received treatment compared to placebo.

Overall, these two phase III trials, show significant superiority of BG12 to placebo on almost all end points. All clinical and MRI parameters showed a trend towards a higher efficacy of BG12 compared with glatiramer acetate, these differences did not reach significance. The safety profile of BG12 is well-known from its use in patients with psoriasis. Tolerability maybe a problem, as 15% of patients initially experience diarrhoea and up to 30% experience flushing. BG12 seems to be at least equally effective as, if not more effective than, established injectables with an excellent safety profile. If BG12 receives approval as a first line therapy for RRMS, it will significantly change the clinical relevance of established injectables.

Limmroth V

Nat Rev Neurol. 2012 Nov 13. [Epub ahead of print]

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