Results of Phase 3 DEFINE and CONFIRM Studies Support Dimethyl Fumarate’s Potential as a Strong Option for MS Treatment
Data from the Phase 3 DEFINE and CONFIRM studies show that dimethyl
fumarate (240 mg), administered twice daily (BID) or three times daily
(TID), demonstrated significant and clinically meaningful reductions in
MS relapses and brain lesions in patients with relapsing-remitting
multiple sclerosis (RRMS) compared to placebo, as well as showed benefit
in slowing the progression of the disease. Dimethyl fumarate is
currently under review by regulatory authorities in
“The publication of both dimethyl fumarate pivotal studies in NEJM is
another achievement for this important investigational therapy,” said
DEFINE and CONFIRM Efficacy Results
Together, the DEFINE and CONFIRM manuscripts in NEJM summarize the positive Phase 3 clinical data set for dimethyl fumarate, which formed the foundation for its regulatory filings around the world.
DEFINE was a two-year global study that evaluated dimethyl fumarate (240 mg, BID or TID) compared to placebo in people with RRMS. Results showed that both dimethyl fumarate BID and TID met the study’s primary endpoint by significantly reducing the proportion of patients who relapsed by 49 percent and 50 percent (p<0.0001 for both; reported in NEJM as <0.001 due to journal requirement that p-values smaller than 0.001 be reported as p<0.001), respectively, at two years compared to placebo. Both dosing regimens also met all secondary endpoints in the study.
“Because MS is a chronic disease, we look for treatment options that not
only control relapses but also slow patients’ disease progression for as
long as possible,” said
Like DEFINE, CONFIRM was a two-year global clinical trial that investigated dimethyl fumarate (240 mg, BID or TID) versus placebo in people with RRMS. The study also included an active reference comparator of glatiramer acetate (GA; 20 mg subcutaneous daily injection) versus placebo. Results showed that both dimethyl fumarate BID and TID met the study’s primary endpoint by significantly reducing annualized relapse rate (ARR) by 44 percent and 51 percent (p<0.0001 for both; reported in NEJM as p<0.001 due to journal requirement that p-values smaller than 0.001 be reported as p<0.001), respectively, versus placebo at two years. In addition, both dosing regimens of dimethyl fumarate met all secondary relapse and magnetic resonance imaging (MRI) endpoints in the study. While not statistically significant, dimethyl fumarate showed a clinically meaningful reduction in 12-week confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS).
The GA data versus placebo in CONFIRM were generally consistent with its product labeling.
“Results of the CONFIRM study were consistent with those of DEFINE,
demonstrating that oral dimethyl fumarate significantly reduced MS
disease activity compared to placebo and has a strong safety profile,”
said
* Dr.
The CONFIRM manuscript in NEJM also includes data from a post-hoc efficacy analysis that directly compared dimethyl fumarate to GA treatment. While CONFIRM was not designed for a formal statistical comparison of GA versus dimethyl fumarate treatment, this post-hoc analysis was included because it may provide helpful information regarding dimethyl fumarate’s efficacy compared to an approved therapy for MS.
DEFINE and CONFIRM Safety Results
In DEFINE and CONFIRM, the safety profile for the dimethyl fumarate BID and TID treatment groups was similar. The overall incidence of adverse events (AEs), serious adverse events (SAEs) and AEs leading to study discontinuation was similar among the dimethyl fumarate and placebo groups in both studies.
In both studies, AEs that occurred more commonly with dimethyl fumarate treatment were flushing and gastrointestinal (GI) events. Flushing and GI events had the highest incidence in the first month of the study and decreased thereafter. The most frequently reported SAE across all treatment groups in both studies was MS relapse.
There was no increase in serious infections or malignancies in the dimethyl fumarate groups compared to placebo in either study. There were no opportunistic infections in the dimethyl fumarate groups. Laboratory analysis in both studies found mean white blood cell counts (WBC) and lymphocyte counts decreased during the first year in dimethyl fumarate-treated patients and then plateaued, remaining within the normal range throughout.
The full manuscripts, called “Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis” (DEFINE) and “Placebo-Controlled Phase 3 Study of Oral BG-12 or Glatiramer in Multiple Sclerosis” (CONFIRM), can be found on the NEJM website at http://www.nejm.org.
About DEFINE
DEFINE (Determination of the Efficacy and safety of
oral Fumarate IN rElapsing-remitting
MS) was a global, randomized, double-blind, placebo-controlled,
dose-comparison study to determine the efficacy and safety of dimethyl
fumarate (240 mg, BID or TID) and enrolled 1,237 people with RRMS. The
primary objective was to determine if dimethyl fumarate was effective in
reducing the proportion of relapsing patients at two years. Secondary
endpoints included reduction in the number of new or newly enlarging
T2-hyperintense lesions and new gadolinium-enhancing (Gd+) lesions as
measured by MRI, reduction in ARR, and reduction of disability
progression as measured by EDSS. Additional endpoints included the
safety and tolerability of dimethyl fumarate. Detailed results from
DEFINE were presented at the 5th Joint Triennial Congress of
the European and Americas Committees on Treatment and Research in
Multiple Sclerosis (ECTRIMS and ACTRIMS) in
About CONFIRM
CONFIRM (COmparator and aN oral Fumarate In Relapsing-remitting
MS) was a global, randomized, double-blind, placebo-controlled,
dose-comparison study to determine the efficacy and safety of dimethyl
fumarate and enrolled 1,430 people with RRMS. The study evaluated two
dose regimens of dimethyl fumarate, 240 mg BID and 240 mg TID, as well
as a reference comparator of GA (20 mg subcutaneous daily injection).
Both dimethyl fumarate and GA groups were evaluated versus placebo. The
primary objective was to determine whether BG-12 was effective in
reducing the rate of clinical relapses at two years. Secondary endpoints
at two years included reduction in: the number of new or newly enlarging
T2-hyperintense lesions and the number of non-enhancing T1-hypointense
lesions (MRI scans were obtained at a cohort of sites); the proportion
of patients who relapsed; and in progression of disability as measured
by EDSS. Safety and tolerability of BG-12 were also assessed. Detailed
results from CONFIRM were presented at the 64th Annual
Meeting of the
About Dimethyl Fumarate
Dimethyl fumarate, also known as BG-12, is an investigational oral therapy in late-stage clinical development for the treatment of relapsing-remitting multiple sclerosis (RRMS), the most common form of MS. Dimethyl fumarate is the only currently known investigational compound for the treatment of RRMS that has experimentally demonstrated activation of the Nrf-2 pathway.
In 2011 and 2012,
About Biogen Idec
Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hemophilia and autoimmune disorders. Founded in 1978, Biogen Idec is the world’s oldest independent biotechnology company. Patients worldwide benefit from its leading multiple sclerosis therapies, and the company generates more than $5 billion in annual revenues. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com.
Safe Harbor
This press release includes forward-looking statements, including
statements about the commercialization of BG-12 (dimethyl fumarate) in
MS. These forward-looking statements may be accompanied by such words as
"anticipate," "believe," "estimate," "expect," "forecast," "intend,"
"may," "plan," “potential,” "will" and other words and terms of similar
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including obtaining regulatory approval, the occurrence of adverse
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Source:
MEDIA CONTACT:
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781-464-3260
or
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