[HTML][HTML] Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis
New England Journal of Medicine, 2012•Mass Medical Soc
Background BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing–
remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or
glatiramer acetate). Methods In this phase 3, randomized study, we investigated the efficacy
and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with
placebo in patients with relapsing–remitting multiple sclerosis. An active agent, glatiramer
acetate, was also included as a reference comparator. The primary end point was the …
remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or
glatiramer acetate). Methods In this phase 3, randomized study, we investigated the efficacy
and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with
placebo in patients with relapsing–remitting multiple sclerosis. An active agent, glatiramer
acetate, was also included as a reference comparator. The primary end point was the …
Background
BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing–remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate).
Methods
In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing–remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate.
Results
At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T2-weighted hyperintense lesions (all P<0.001) and new T1-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T2-weighted hyperintense lesions (both BG-12 doses), and new T1-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12.
Conclusions
In patients with relapsing–remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.)
The New England Journal Of Medicine