Biogen Idec published results from a pair of two-year global Phase III clinical trials showing promising results for its experimental drug oral BG-12 (dimethyl fumarate) for the most common form of multiple sclerosis.
Both studies, published Wednesday in The New England Journal of Medicine, covered 240 mg doses of BG-12 administered twice daily (BID) or three times daily (TID) in patients with relapsing-remitting multiple sclerosis (RRMS) compared to placebo.
One study, labeled DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS), found that BG-12 BID and TID met the primary endpoint by reducing the proportion of patients who relapsed by 49% and 50%, respectively after two years compared to placebo.
Both dosing regimens also met all of DEFINE’s secondary endpoints, which included reduction in the number of new or newly enlarging T2-hyperintense lesions and new gadolinium-enhancing lesions, reduction in annualized relapse rate, and reduction of disability progression as measured by the Expanded Disability Status Scale. A total 1,237 patients with RRMS were enrolled in DEFINE.
“In DEFINE, dimethyl fumarate demonstrated efficacy, as well as positive safety and tolerability profiles, which is a very attractive combination for an MS treatment,” the study’s lead author, Ralf Gold, Ph.D., professor/chair of the Department of Neurology at St. Josef-Hospital/Ruhr-University in Bochum, Germany.
The other study, labeled CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting MS), emulated DEFINE but added an active reference comparator of glatiramer acetate (GA; 20 mg subcutaneous daily injection) versus placebo.
Both BG-12 BID and TID met that study’s primary endpoint by significantly reducing the rate of clinical relapses at two years by 44% and 51%, respectively. Both also met all secondary relapse and magnetic resonance imaging endpoints in the study, which also showed BG-12 achieving a clinically meaningful—but not statistically significant—reduction in 12-week confirmed disability progression.
Secondary endpoints at two years included reduction in the number of new or newly enlarging T2-hyperintense lesions and nonenhancing T1-hypointense lesions, as well as in the proportion of patients who relapsed, and in progression of disability.
CONFIRM also includes data from a post-hoc efficacy analysis directly comparing BG-12 to GA treatment, with investigators reasoning that it may provide helpful information regarding the drug’s efficacy compared to an approved therapy for MS. A total 1,430 people with RRMS were enrolled in CONFIRM.
In both studies, the most frequently reported serious adverse event across all treatment groups was MS relapse, while the most common adverse events were flushing and gastrointestinal events, with most occurring in the first month and decreasing afterward.
[Read the DEFINE study here: http://www.nejm.org/doi/full/10.1056/NEJMoa1114287?query=featured_home]
[Read the CONFIRM study here: http://www.nejm.org/doi/full/10.1056/NEJMoa1206328?query=featured_home ]