FDA Approves Another Oral Treatment for MS
The U.S. Food and Drug Administration has approved Tecfidera™ capsules (dimethyl fumarate, Biogen Idec –formerly “BG-12”) as a first-line disease-modifying therapy for people with relapsing forms of MS, making it the third oral disease-modifying therapy approved for relapsing forms of MS.
Tecfidera™ is related to Fumaderm which has been used in Germany for over 20 years to treat people with psoriasis. While its mechanism of action is not well understood, Tecfidera™ is thought to favorably impact the TH1 and TH2 lymphocyte profile inhibiting inflammatory cells and suppressing damaging macrophage activity. It is also believed to have anti-oxidant properties that could be protective against damage to the brain and spinal cord.
Two large scale clinical trials of Tecfidera taken twice daily showed that Tecfidera significantly reduced relapses and disease activity on MRIs, and in one trial it reduced progression of disability. The DEFINE study involved 1,200 individuals for 2 years and showed 50% reduction in the proportion of people who relapsed during the study period. The drug decreased disease progression by 38%. The CONFIRM study involved 1,400 people and compared 2 doses of Tecfidera with placebo and with Copaxone for 2 years. The reduction in relapse rate was 44% for those on Tecfidera and 29% for those on Copaxone compared to placebo. Results in secondary endpoints included significant reductions in disease activity on MRI and the proportion of patients experiencing relapses in the Tecfidera groups versus placebo. Disability progression was not reduced significantly in the Tecfidera groups compared to the placebo group.
About 40 % of the clinical trial participants experienced flushing (which can create a sensation of heat or itching and a red blush on the skin) and some experienced gastrointestinal events (such as diarrhea, nausea, and upper abdominal pain) during the first month of treatment. These symptoms decreased after the first month. On rare occasions, Tecfidera also reduced blood lymphocyte (white blood cell) counts, but there were no significant infections reported. Liver enzyme tests were elevated, but there were no reports of significant liver injury or liver failure.
As the number of FDA approved drugs continues to grow, and there remain a good number of drugs in the pipeline likely to be approved for marketing in the next few years, MS therapy decisions become more complex for clinicians, those with MS, and those close to them. Everyone needs to be well informed and educated so that thoughtful and appropriate MS care decisions are made. One must be vigilant and understand that there are drugs about which we know much regarding efficacy and safety, and those we know less about. Extension trials of the already existing drugs tell us that our platform drugs continue to perform well. The growing number of agents proven to deter MS is reassuring and the number of emerging therapies is indeed promising.
By Bruce Bebo, PHD
Emerging evidence across the board suggests that exercise doesn’t just keep us physically fit, it helps our brain function better, too. Scientific presentations on exercise, rehabilitation and quality of life issues at the American Academy of Neurology’s annual meeting in March suggest this holds true for people living with multiple sclerosis, as well.
Exercise’s Good Effects
A small study from National Multiple Sclerosis Society-supported scientists at the Kessler Research Institute in New Jersey found that 30 minutes of aerobic exercise done three times a week over three months improved memory and increased the volume of the hippocampus, a part of the brain involved with memory. These preliminary results will hopefully encourage further studies that will yield more definitive conclusions and maybe even recommendations.
Another study examined the potential of longer-term aerobic exercise to build endurance in people with MS. This study involved 60 people split into two groups: people who experienced fatigue and people who did not. Both groups performed individualized endurance exercises using treadmills. After six months, both groups showed improved oxygen consumption. However, those who started out with fatigue showed improvement in their fatigue scores, but it took at least nine months of the program to see a difference. So while you may not feel the effects of exercise at first, persistence can pay off!
Exercises for The Brain
Some very interesting data illustrating how the brain reorganizes to adapt to MS damage was presented by a research team from the San Raffaele Hospital in Milan, Italy. This team looked at the impacts of a 12-week computer-assisted course that focused on training to increase memory and attention (the course was previously reported to improve attention and executive thinking abilities). Using functional MRI, which allows a real-time glimpse of the brain at work, they found indicators that brain activity had increased in specific areas. This improvement appeared to persist at least six months after the training was completed.
Researchers from Milan and from Kessler also reported that people with MS with more “brain reserve” (larger brain size) and more “cognitive reserve” (increasing the ability to withstand or postpone MS-associated decline in cognition with activities such as doing puzzles or playing music) were at lower risk for cognitive changes associated with brain lesions. Even when brain size is accounted for, those with more cognitive reserve appear to have lower risk for cognitive changes.
There’s nothing any of us can do about the size of our brains. But growing evidence suggests that people may be able to build cognitive reserve by engaging in enrichment activities (Words with Friends anyone?). It’s exciting to think that actions we can take, such as some mental and physical training, can actually alter brain circuits, improve brain activity and possibly help slow the progression of MS.
Summaries of the meeting can be viewed on the AAN’s website at www.abstracts2view.com/aan, or visit www.nationalMSsociety.org/research for an overview of MS-related research presented at the meeting.
Bruce Bebo, PhD, is associate vice president of Discovery Research at the National MS Society.