Biogen-Idec have announced positive top-line results from CONFIRM, the second of two pivotal phase 3 clinical trials designed to evaluate the effectiveness of the oral compound BG-12 (dimethyl fumarate) in RRMS's.
BG-12 met the CONFIRM study's primary endpoint by significantly reducing annualized relapse rate (ARR) by:
- 44% for twice daily (BID) dosing (p< 0.0001) and by 51% for three time daily (TID) dosing (p< 0.0001) versus placebo at two years. The CONFIRM study's reference comparator, glatiramer acetate (GA; 20 mg subcutaneous daily injection), reduced the ARR by 29% (p< 0.02) compared with placebo at two years.
In addition to significantly reducing ARR, BG-12 met all secondary relapse and MRI endpoints for both dose regimens. Results for the BG-12 and GA treatment groups at two years compared with placebo included:
- BG-12 reduced the number of new or newly enlarging T2-hyperintense lesions by 71% for BID (p<0.0001) and by 73 percent for TID (p<0.0001), while GA provided a 54 percent (p<0.0001) reduction.
- BG-12 reduced new T1-hypointense lesions by 57 percent for BID (p<0.0001) and by 65 percent for TID (p<0.0001), while GA provided a 41 percent (p<0.003) reduction.
- BG-12 reduced the proportion of patients who relapsed by 34 percent for BID (p<0.003) and by 45 percent for TID (p<0.0001), while GA provided a 29 percent (p<0.01) reduction.
- Initial results showed that BG-12 reduced 12-week confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS) by 21% for BID and 24% for TID at two years compared to placebo, and GA reduced confirmed disability progression by 7%. These results were not statistically significant, they may be attributable to the unexpectedly low rate of disease progression in the placebo group, which was approximately half of what has been seen in other clinical trials of approved and experimental multiple sclerosis (MS) therapies.
Both dose regimens of BG-12 showed favorable safety and tolerability profiles, which were similar to those seen in the first phase 3 or DEFINE study. Overall, the incidence of adverse events (AEs), serious adverse events (SAEs) including serious infections, and discontinuations due to AEs were similar across all study groups, including placebo. The incidence of hepatic and renal events was also comparable among all study groups. The most common AEs in the BG-12 groups were flushing and GI events. There were no malignancies in the BG-12 groups.
"This is very good news for people with RRMS. What is now needed is a trial of BG12 in progressive MS. Hopefully Biogen-Idec will prioritise this ASAP."
"I am surprised that glatiramer acetate (Copaxone) did so poorly in this study; it has a history of doing well in head-2-head studies."
Source: Biogen-Idec Press Release 26th Oct 2011
CoI: Multiple