240 mg of Dimethyl Fumarate (BG-12) taken orally two or three times a day showed reduced relapses by about half in patients with relapsing-remitting multiple sclerosis (PRMS) compared to those on placebo, Biogen Idec announced after publishing results from a Phase 3 DEFINE clinical trial. Relapse reduction was 49% for those taking the medication twice a day (BID) and 50% for those on three doses per day (TID) two years after treatment began.
BID = bis in die (Latin), meaning "twice a day". TID = ter in die (Latin), meaning "three times a day".
Results of the DEFINE trial were presented in Amsterdam at the 5th Joint Triennial Congress of the European and Americas Committees on Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS).
Doug Williams, Ph.D., Executive Vice President of Research and Development at Biogen Idec, said:
"The significant clinical and radiological responses in DEFINE are further evidence that BG-12 may become an oral therapy of choice for MS patients. Results from our second Phase 3 trial, CONFIRM, will provide additional insight into BG-12's profile, as well as a comprehensive data set to further discussions with regulatory authorities. We anticipate releasing top-line data from CONFIRM later this year."
Dimethyl Fumarate, known as BG-12, molecular formula C6H8O4, was tested on patients with MS in the first of two Phase 3 clinical trials (DEFINE). The aim was to determine its efficacy and safety. The drug met its primary and secondary endpoints in the trial for both doses - BID and TID.
Not only was there a considerable reduction in the percentage of patients who relapsed, there was also a substantial drop in ARR (annualized relapse rate) as well as the risk of disability progression at two years, compared to those in the placebo group.
Below are some highlighted data from the DEFINE trial:
- BG-12 Group BID - they experienced a reduction in relapse risk of 49% compared to those in the placebo group
- BG-12 Group TID - they experienced a reduction in relapse risk of 50% compared to the MS patients in the placebo group
- BG-12 Group BID - they had a 53% lower ARR compared to the patients on placebo
- BR-12 Group TID - they had a 48% lower ARR compared to those on placebo
- BR-12 Group BID - their disability progression risk was 38% lower compared to those on placebo
- BR-12 Group TID - their disability progression risk was 34% lower than those on placebo
"BG-12 may be a valuable treatment option for MS patients, combining strong efficacy, a favorable safety profile and oral administration. Preclinical research has shown that BG-12 has anti-inflammatory and neuroprotective effects. If the clinical responses seen in DEFINE are replicated in its second Phase 3 trial, BG-12 has the potential to provide a new approach to treating MS and be an important step forward for patients."
All the patients in the trial underwent MRI (magnetic resonance imaging) scans at baseline, 24 weeks, 12 months and 24 months to determine the number of gadolinium-enhancing (Gd+) lesions, T2 hyperintense lesions, and and T1 hypointense lesions (a tertiary endpoint).
The MRI scans at 24 months findings revealed the following:
- BG-12 Group BID - the mean number of new or newly enlarging T2 hyperintense lesions dropped by 85%
- BG-12 Group TID - the mean number of new or newly enlarging T2 hyperintense lesions dropped by 74%
- BG-12 Group BID - the mean number of Gd+ lesions dropped by 90%
- BR-12 Group TID - the mean number of Gd+ lesions dropped by 73%
- BR-12 Group BID - mean number of new T1 hypointense lesions fell by 72%
- BR-12 Group TID - mean number of new T1 hypointense lesions fell by 63%
"The BG-12 program further demonstrates Biogen Idec's commitment to developing innovative therapies to address unmet needs in the MS community. BG-12's distinct mechanism of action, combined with strong efficacy and safety data, position it as a potentially valuable option for MS patients and a further growth driver for Biogen Idec."
The safety profiles for those in the BID and TID Dimethyl Fumarate groups were similar. The overall incident rate for adverse events and serious adverse events and events that led to dropping out of the study were similar among the placebo and Dimethyl Fumarate groups. The most common adverse events across all groups were MS relapse, nasopharyngitis, flushing, fatigue, diarrhea, and headache.
21% of those on placebo reported a serious adverse event, compared to 17% among those in the treatment group. The most common serious adverse event was MS relapse. During the study treatment period nobody died, infection or serious infection rates did not increase, neither did malignancies or opportunistic infections.
Written by Christian Nordqvist