MS research 2013

Editor's Notes

• #9: 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. This makes the third oral therapy approved for relapsing MS, and the tenth disease-modifying treatment available in the U.S.  “The approval of Tecfidera is an important expansion of therapeutic options, and increases our ability to find effective and tolerable treatment solutions for individual patients,” said Bruce A. Cohen, MD, Professor, Davee Department of Neurology and Clinical Neurosciences at Northwestern University’s Feinberg School of Medicine, and Chair of the National MS Society’s National Medical Advisory Committee. “As with all newly-approved treatments, we will learn more about the benefits and safety of Tecfidera over time,” he added. “The approval of Tecfidera is encouraging news for people who have relapsing forms of MS,” noted Timothy Coetzee, PhD, Chief Research Officer at the National MS Society. “Having ten disease-modifying therapies available for relapsing forms of MS further motivates us to gather the forces of the global community to make similar strides for people with progressive forms of MS, for whom there are fewer options.” Read more about the International Progressive MS Collaborative (.pdf) Read the FDA’s press release. Download patient information about Tecfidera. About Tecfidera: Multiple sclerosis involves immune system attacks against brain and spinal cord tissues. Although its exact mechanism of action is not known, Tecfidera is thought to inhibit immune cells and molecules, and may have anti-oxidant properties that could be protective against damage to the brain and spinal cord. A chemically related compound, called Fumaderm (dimethyl fumarate and fumaric acid esters), has been used for decades in Germany to treat acute flare-ups of psoriasis. Tecfidera is a new, different formulation of dimethyl fumarate that was developed by Biogen Idec specifically for the treatment of multiple sclerosis. Potential benefits: Twice-daily Tecfidera was shown in clinical trials to significantly reduce relapses and disease activity on MRIs, and in one trial it reduced progression of disability. The FDA’s approval was based largely on results of two large-scale phase III studies of Tecfidera capsules, called DEFINE and CONFIRM, which were conducted in people with relapsing-remitting MS. The results were published in 2012. Read a summary In the DEFINE trial, there was a significant reduction in the proportion of people on Tecfidera who experienced relapses at 2 years, compared with those on inactive placebo. For those on the approved twice-daily dose, 27% experienced relapses, versus 46% of those on placebo -- a 49% reduction in the risk of relapse. All secondary outcomes were also met in the Tecfidera groups, including significant impact on disease activity detected with MRI, and reduction in the risk of confirmed progression of disability (detected by the EDSS, a standard scale that measures disability). The proportion of those who progressed over two years was 16% for twice-daily Tecfidera versus 27% for placebo -- a 38% reduction in risk of disability. In the CONFIRM trial, there was a significant reduction in the average annual number of MS relapses (annualized relapse rate, or ARR) in the Tecfidera groups versus placebo. For those on the approved twice-daily dose, ARR was reduced by 44% versus 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. Potential risks and screenings: The most common adverse events experienced by people taking Tecfidera during the trials were flushing (which can create a sensation of heat or itching and a red blush on the skin) and gastrointestinal events (such as diarrhea, nausea, and upper abdominal pain). During the clinical trials, up to 40% of participants experienced flushing, and some experienced gastrointestinal events. The incidence of these events was highest in the first month of treatment, decreasing thereafter. Tecfidera reduced blood lymphocyte (white blood cell) counts but no significant or severe infections were reported. Liver enzyme tests were elevated, but there were no reports of significant liver injury or liver failure.  Before starting treatment, the FDA recommends that a person’s health care provider assess a recent (within 6 months) blood cell count, and repeat the blood cell count annually thereafter. Before starting treatment with Tecfidera, women should talk to their health care providers if they are pregnant or planning to become pregnant. Taking a disease-modifying therapy is currently the best way to reduce MS disease activity and future deterioration. Selecting an MS therapy should be done by people with MS in collaboration with their MS doctors, taking into account a variety of factors, including the effectiveness of any therapy they are currently using, and weighing potential risks and benefits, costs and lifestyle factors.
• #10: There is not unanimity as to what constitutes excessive disease activity
• #13: It is worth remembering that not all injectable DMTs have comparable effects on MRI or clinical outcome which must be considered when comparison trials are carried out
• #18: Bizarre symptom complex. Acute transient cerebellar dysfunction affecting all the mm of the body including articulation Few seconds to min nystagmus
• #23: The National MS Society’s Fast Forward drug development subsidiary is partnering with Accera, Inc., and the University of Miami’s Miller School of Medicine in a clinical trial to determine potential benefits  of Accera’s medical food, Axona® (caprylic triglyceride),  on cognitive impairment in people with MS. Funding to test this novel dietary approach to a troubling MS symptom provides University of Miami with funding over a 36-month period, and like other Fast Forward research partnerships, payments will be contingent upon the completion of specific milestones achieved during the trial. Novel Approach: Axona is an FDA-regulated “medical food.” Axona has been approved by the FDA for management of biological processes associated with mild to moderate Alzheimer’s disease.  As a medical food, Axona is intended to be used under physician supervision. It has not been approved by the FDA for use in MS. Cognitive problems are a common symptom in individuals with MS and may have a negative impact on relationships, work, and quality of life. Treatment options are limited. Glucose (a type of sugar) is used to fuel the cells of the healthy brain. For people with neurological conditions such as MS, glucose may not be converted into energy as efficiently as it would be in a healthy brain, which can lead to a decrease in cognitive function. Axona may work to bypass this problem by providing an alternative energy source that is processed in the liver and used by the brain. This placebo-controlled study will be conducted by researchers at the University of Miami MS Center and will enroll 158 people with MS to determine whether Axona can help restore cognitive function to people with MS. Researchers are recruiting trial participants in the local South Florida area who have MS and have experienced cognitive changes. For more information or to schedule a screening visit, contact the research Coordinator, Gloria Rodriguez at 305-243-8052 or by email atGRodriguez13@med.miami.edu.
• #24: National MS Society is pleased to report that Canbex Therapeutics Ltd. has completed a $3.2 million (£2.1m) fundraising round that will enable it to finish the early development of a potential therapy for the debilitating muscle spasms known as spasticity in MS. Merck Serono Ventures led the financing for this round. This success leverages an initial investment in Canbex in 2010 by the National MS Society’s Fast Forward drug development arm, validating the concept of seeding early development to speed therapies to people with MS.  Spasticity is a common and often painful symptom of MS that involves feelings of stiffness, tightness or sudden movements caused by a wide range of involuntary muscle spasms. Many of the current treatments for spasticity can cause significant side effects, such as muscle weakness, sedation or mood alteration that can limit their application in MS. Canbex aims to develop a new therapy called VSN16R in hopes of creating a better treatment for spasticity affecting people with all forms of MS, including progressive MS.
• #25: Amiloride in progressive MS: This oral blood pressure medicine was tested in a small study of 14 people with primary progressive MS because it had been shown previously to have nerve-protecting (neuroprotective) properties. Dr. Tarunya Arun of Oxford University, with colleagues in the UK and Netherlands, reported after 3 years, treatment with amiloride resulted in a reduction of brain shrinkage associated with progressive disease, compared to what was experienced before treatment. Further testing is getting underway in a larger study in the UK, which the National MS Society is helping to support through the UK MS Society. (Abstract S31.002)
• #33: We don’t know yet why some people’s MS progresses slowly and others experience rapid progression
• #36: Also the MS study out of Texas published Mar 2013-The team concludes that they find less CCSVI than previously reported by other groups, and that their findings do not support the idea that CCSVI is causally related to MS. They are now focusing on whether ultrasound can be complemented or supplanted by MRV and/or transluminal venography.
• #37: 132 pounds