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Archive for the category “National Multiple Sclerosis Society”

New Research on Lemtrada Reveals Insights into the Cause of Potential Side Effects

Researchers in the U.K. have evaluated additional findings about the immune-system impacts of Lemtrada® (alemtuzimab, Sanofi Genzyme), a disease-modifying therapy for treating people with relapsing MS.

The team used data from phase 3 clinical trials submitted to the European Medicines Agency during the drug’s successful approval process. Some of this data was previously reported at medical meetings and in Lemtrada’s prescribing information.

Among their findings, they report that Lemtrada caused long-term reduction of specific immune cells (memory B and T cells, including regulatory T cells). They also found that the body rapidly repopulated an overabundance of immature B cells.

They propose that the blockade of memory B and T cells drives the beneficial effects of Lemtrada.

They also speculate that the known potential side effect for autoimmune thyroid disease and other autoimmune disorders may be triggered by the overabundance of immature B cells that occurs when there are few regulatory T cells to keep them in check.

Studies like this one, which reveal more information about a therapy’s mode of action, are important and may also lead to insights about how to reduce side effects.

Drs. Klaus Schmierer, David Baker and others at the Queen Mary University of London report their findings in JAMA Neurology, published online June 12, 2017.

Read the open-access paper in JAMA Neurology
Read about Lemtrada
Read more about treating MS

Lemtrada is a registered trademark of Sanofi Genzyme

Interesting Results…

Gene That Boosts Resistance to Malaria linked to Susceptibility to MS and Lupus in Sardinia

Researchers from Italy found a strong association between the gene that instructs the molecule “BAFF” and susceptibility to MS and lupus in studies of nearly 6,000 people in Sardinia. The BAFF gene is crucial to activation of immune B cells and is also associated with resistance to malaria. Malaria was common in Sardinia until it was eradicated in 1950. The rates of MS and certain immune-mediated diseases are high in Sardinia. Further research is necessary to confirm whether this high rate is related to BAFF, and whether MS could be treated by a therapy that targets BAFF.

Read more about this study from the Genetic Literacy Project

Read the scientific summary of the paper in The New England Journal of Medicine

Read more about efforts to end MS forever

 
 

Novel Protein Identified Inside Cells During MS Inflammation May Help Explain Nerve Damage

Researchers from the University of Alberta in Canada report that levels of Rab32 – a protein that directs traffic between cell organs – are increased in sites of active inflammation in brain tissue obtained from people with MS and in mouse models of MS-like disease. This increase was linked to the destruction of nerve cells. If the results are confirmed, this knowledge could explain part of the neurodegenerative process that leads to progression of disability in MS and could be a target for development of effective MS treatments.

Read more on ReliaWire
Read the open access paper in Journal of Neuroinflammation
Read more about Research to stop MS in its tracks

Researchers Recruiting African Americans with MS Across the U.S. for Genetics Studies – Key to finding cause of MS and better treatments

Rationale: Genes are known to play a role in determining who is susceptible to developing multiple sclerosis, and may also influence the course of the disease. People living with MS can make a difference in studies searching for these genes by donating their DNA from blood samples. Identifying the exact location of MS genes could help determine who is at risk for developing the disease and may provide clues to its cause, prevention, and better treatment. Focusing on ethnic groups with lower susceptibility to MS (such as African-Americans) and higher susceptibility (such as individuals of Northern European descent), and searching for what is common and what is different in their genes may help pinpoint regions that contain MS genes. Large numbers of participants are needed to accelerate this research.

Details: It is not necessary to travel to San Francisco to participate in this study. Once an individual has completed the initial online intake form and has agreed to participate, they are emailed the links to two additional online forms and sent a kit via express mail. The kit includes a consent form, a health information privacy form, and a medical records release form. The kit also includes everything necessary for the blood draw, which can be taken to your local Quest Diagnostics Lab, where the blood can be drawn and then returned in a prepaid envelope to the UCSF MS Genetics Lab. There is no cost to the study participants.

Contact: To participate or request additional information, please complete our brief intake survey.

OR you may contact us directly:

Clinical Research Coordinator
UCSF Multiple Sclerosis Genetic Susceptibility Project
675 Nelson Rising Lane, Suite 235A, Box 3206
San Francisco, CA 94158
Email: msdb@ucsf.edu
Website: http://msgenetics.ucsf.edu/index.html
Toll Free Phone: 1-866-MS-Genes (1-866-674-3637)

Australian Team Finds Possible Molecular Pathway for MS Progression

Researchers from Australia report that the amount of molecules in a sequence of chemical reactions called the kynurenine pathway differs between people with MS and healthy controls, and between people with relapsing-remitting and progressive forms of MS. The kynurenine pathway is activated by chronic inflammation, and its activation may be involved in nerve damage and MS progression.  The kynurenine pathway has also been implicated in other neurological and psychiatric disorders. The MS-specific findings, and the potential use of the kynurenine pathway in a diagnostic test, will need to be explored in additional studies.

This work was funded by the National Health and Medical Research Council and Multiple Sclerosis Research Australia. The researchers used several repositories to complete these experiments – the Accelerated Cure Project for MS, The Human Brain and Spinal Fluid Resource Center (which is sponsored by the National MS Society, among others), and the Tasmanian MS Longitudinal Study.

Study Finds That Some Family Members of People with MS Show Possible Early Signs of the Disease without Symptoms

Summary

  • As part of a large-scale “Genes & Environment in MS” (GEMS) study to understand factors that lead to the development of multiple sclerosis, researchers analyzed the genes and backgrounds of individuals who had no symptoms of MS, but who had close family members with MS.
  • Based on that analysis, researchers identified a group of 40 women at higher risk for developing MS, and 25 women at lower risk. Extensive neurological testing and MRI scanning uncovered possible neurological abnormalities in the higher risk group, and MRI abnormalities in a small proportion of both groups.
  • “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation,” explains co-author Dr. Phillip De Jager. “Family members should be reassured that the vast majority of family members will not develop MS.”
  • The team (including Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).
  • This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Background: An individual’s risk of developing MS increases if a close family member has MS. There is currently no way to predict which family members will develop MS. The goal of the Genes & Environment in MS (GEMS) study is to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.  Researchers are recruiting 5,000 subjects who have at least one first-degree relative with a diagnosis of MS. The GEMS Study is gathering genetic material (DNA) and environmental exposure history from participants as well as blood samples and brain magnetic resonance imaging (MRI) as an option. Investigators are classifying participants using the Genetic and Environmental Risk Score for MS Susceptibility (GERSMS), an experimental approach which incorporates genetic information and environmental exposures to identify people at higher or lower risk of developing MS.

The Study: As part of this large-scale, ongoing study, researchers looked at 65 women who are first-degree relatives of people with MS. The GERSMS indicated that 40 of these women were at higher risk of developing MS, and 25 women were at lower risk of developing MS. These women underwent a comprehensive neurologic examination and MRI scans.

Women in the higher risk group had less than normal vibration sensitivity in their big toes, a finding that indicates potential nerve dysfunction. A small percentage of the women in both groups had more MRI abnormalities associated with MS than one would expect to find in the general population.

The team (Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, Boston, MA, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).

This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Next Steps:  In this study, women at high risk for MS showed possible early manifestations of the disease. “The goal of the Genes & Environment Study is to understand the sequence of events that leads someone to develop MS,” explains co-author Dr. De Jager. “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation. Family members should be reassured that the vast majority of family members will not develop MS.” He notes that the study did not test the possibility of preventive strategies, such as vitamin D supplementation.  “Taking vitamin D is good for bone health, and MS family members should discuss taking such supplements with their physician.”

Read more about research to find the genetic and environmental underpinnings of MS

 

New Study: Resilience in People with Chronic Disease is Linked to Social Satisfaction and Quality of Life – Not Physical Function

Summary

  • A survey of more than 1500 people with MS and other chronic diseases shows that resilience (the ability to solve problems and bounce back from difficult situations) is linked to satisfaction with social roles (such as work and family responsibilities) and quality of life, but not to physical function.
  • Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.  Learn more about how the resilience factor can help you to thrive. Watch an education program on Resilience: Addressing the Challenges of MS.
  • The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Background: Research on psychosocial issues forms a cornerstone of finding life-changing solutions for people with MS. MS can have a significant impact on a person’s emotions, not only because MS is unpredictable and challenging to live with, but because it affects parts of the brain that control mood. This study specifically looked at factors that can affect resilience (i.e., the ability tackle problems, find solutions and bounce back from difficult situations).

The Study: The team reviewed information on 1574 people with MS, muscular dystrophy, post poliomyelitis syndrome, and spinal cord injury, which was gathered from an ongoing survey that is tracking people in the United States who are aging with physical disabilities. Information was collected on resilience using a clinical scale, and on other factors (including physical function, satisfaction with social roles – meaning work and family responsibilities, and quality of life) using questionnaires that assess how people report their own health status.

The results suggest that people who reported significantly greater satisfaction with social roles and significantly greater quality of life had significantly higher resilience. This relationship was slightly different between men and women, in that men who expressed greater levels of satisfaction with social roles reported higher levels of resilience. Surprisingly, noted the authors, resilience was not significantly greater in people who reported better physical function.

The team (Samuel Battalio, BS, and colleagues at the University of Washington) has published results in Archives of Physical Medicine and Rehabilitation (2016 Dec 16).

Next Steps: The authors note that resilience is complex, and that further research could help uncover particular aspects of resilience that may be most beneficial to individuals.  Understanding factors that promote resilience may help people with MS to not only cope with unpredictable changes in health and abilities, but to thrive in spite of these changes.

There are behaviors that can help promote individuals’ resilience:

New Results Show that Magnetic Stimulation of Brain May Improve Working Memory and Brain Connectivity in People with MS

Summary

  • People with MS, but not healthy controls, showed improvements in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another), after treatment with Repetitive Transcranial Magnet Stimulation (rTMS). This device generates electromagnet pulses that stimulate brain activity.
  • rTMS may have a future role in cognitive rehabilitation in people with MS, but further, larger studies are necessary to confirm the safety and effectiveness of this intervention and its long-term effects.
  • The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry (Published Online First: 14 December 2016).

Background: Repetitive Transcranial Magnet Stimulation (rTMS) was approved by the FDA as a treatment for major depression. A device that generates electromagnet pulses is placed on the scalp with the idea of stimulating specific brain activity. Studies have shown that people with MS who received rTMS showed significant decreases in depression. This team looked at whether rTMS improved working memory (short-term memory needed for tasks such as mental arithmetic), which can be affected in people with MS.

The Study: Investigators administered rTMS – or a “sham” version of lower intensity – to an area of the brain associated with working memory in17 people with MS and 11 healthy controls. None of the participants showed signs of impaired memory at the outset of the study. A potential adverse event of rTMS is seizures, so participants were excluded if they were taking medicine that put them at risk for seizures, or had MS brain lesions in particular areas. Before and after, participants underwent imaging and extensive neuropsychological testing aimed at investigating memory. They also completed a working memory task while undergoing functional MRI, which measures brain activity during tasks.

At the beginning of the study, there were no differences in working memory between people with MS and controls. After treatment, the results suggested improvements among people with MS in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another). These changes were not seen in controls.

The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry

Next Steps: The authors comment that this small study implies that rTMS may play a future role in cognitive rehabilitation in people with MS. However, the study is limited by the small sample size and the fact that participants did not have obvious cognitive problems. Further studies that address these factors are necessary to confirm the safety and effectiveness of this intervention for people with MS and its long-term impact on day to day activities.

Read more about cognitive changes that affect people with MS

 

World’s Largest MS Research Conference Highlights Advances in Progressive MS, Gut Microbiome, Managing Symptoms, and New Approaches to Restoring Function

Results from clinical trials, including new approaches to treating progressive MS, lifestyle and wellness research and myelin repair strategies were among more than 2,000 presentations made at the European Committee for Treatment and Research in MS (ECTRIMS) meeting held in London, England in September.
The world’s largest gathering of MS researchers convened more than 9,000 scientists and clinicians and industry representatives from across the globe, including many National MS Society-funded researchers, meeting and presenting on cutting-edge MS research progress. In addition, the European Rehabilitation in MS network met jointly with ECTRIMS this year.

During the conference, the International Progressive MS Alliance announced new investments of over $14 million US dollars to support three Collaborative Network Awards. These international teams were selected to accelerate the pace of research in key areas to speed new therapies for progressive MS.

Below are highlights of presentations focused on stopping MS, restoring function, and ending MS forever. In most cases, studies presented are considered preliminary. Many will be analyzed more thoroughly, and likely published in peer-reviewed journals.

STOPPING MS

Many presentations showed continued benefits of available therapies and longer-term safety information, as well as more evidence that early and ongoing treatment with a disease-modifying therapy has long-term benefits for controlling disease activity, delaying accumulation of disability, and protecting quality of life.

Siponimod in secondary progressive MS: More details were presented from a 60-month, phase 3 clinical trial of the experimental oral therapy siponimod (Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS. The trial met its primary endpoint, with those on active treatment showing a modest 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced MRI-detected lesion volume. The medication showed a similar safety profile to others that work by preventing white blood cells from entering the central nervous system. (Abstract #250)

More details from trial of lipoic acid in secondary progressive MS: Dr. Rebecca Spain and colleagues (Oregon Health & Science University) presented results from a small, controlled clinical trial on the oral anti-oxidant supplement called lipoic acid in people with secondary progressive MS. The lipoic acid group had 66% less brain tissue shrinkage, or atrophy, than the group taking inactive placebo pills. This pilot study suggests potential benefits if they hold up in a larger trial. (Abstract #222)

New results on gut bacteria: Efforts are advancing to pinpoint bacteria in the gut that may drive inflammatory immune system activity in MS and others that can suppress it, which may open the door to novel probiotic or other therapeutic approaches to treating MS.

  • Drs. Yan Wang, Lloyd Kasper and colleagues (Dartmouth Medical School and Eastern Washington University) reported that treating mice with the gut-related molecule called polysaccharide A (PSA) expanded a type of immune cells called “Regulatory B cells” (Bregs) which promote an immune response that prevents mice from getting MS-like disease. (Abstract #181) Members of this team also reported that PSA had positive effects in mice with progressive MS-like disease. (Abstract #P465)
  • Dr. Sergio Baranzini (University of California, San Francisco) and other collaborators in the National MS Society-supported MS Microbiome Consortium are analyzing gut bacteria to unearth clues about MS susceptibility and progression. They analyzed bacteria in stool samples from 64 people with MS who had received treatment for MS, and 68 people without MS. Certain bacteria were increased in people with MS, and those bacteria increased immune cells (T helper 1 cells) that are major players in MS immune attacks. Another type of bacteria that could suppress the immune attack was reduced. (Abstract #179)

Disappointing results for nerve-protection approaches: A small two-year clinical trial of fluoxetine (same compound as the anti-depressant Prozac) did not meet its goal of improving walking speed in people with progressive MS. The multi-center team from Belgium is still analyzing other results, such as changes in MRI and cognition. (Abstract #253) Likewise, a trial conducted at the University of Oxford tested the ability of amiloride to protect against nerve damage in people with acute optic neuritis (often an early sign of MS) failed to show any neuroprotective benefit. (Abstract #102) Additional trials of neuroprotective approaches to MS are ongoing.

Vitamin D deficiency and smoking linked to progression: Dr. Maria Isabel Zuluaga and team (Vall d’Hebron University, Barcelona) explored the independent impacts of smoking and vitamin D deficiency in a large group of people followed over time. They found that those with severe vitamin D deficiency (defined as blood levels at less than 8 ng/ml) showed an increased risk for MS disability, and active smokers also had an increased risk for disability progression. (Abstract #252) Graduate student Ms. Eva Rosa Petersen (Danish MS Center, Copenhagen) also found that smoking intensity was linked with higher frequency of relapses among people taking interferon beta. Smoking one pack of cigarettes per day increased relapse rates by 25%. (Abstract #178)

Vitamin D added to Rebif: A large international trial did not show a statistical difference between treatment groups after adding vitamin D (14,000 IU [350 µg] vitamin D3 daily) or placebo to Rebif therapy in relapsing MS, in terms of the percent of participants who were free from disease activity after 48 weeks. Dr. Raymond Hupperts (Orbis Medical Centre, Sittard-Geleen, The Netherlands), who presented results, noted that both groups were stable, which likely contributed to the inconclusive results. (Abstract #166)

Biomarkers under development: Teams are making headway toward having a simple test that can predict a person’s disease course, progression and response to therapy. Dr. Bibiana Bielekova (National Institute of Neurological Diseases and Stroke) and team examined proteins in the spinal fluid of people with neurological diseases, including all types of MS, and identified a “signature” of markers that distinguished MS from other diseases, and also differentiated relapsing MS from progressive MS. (Abstract #219). Other investigators also reported progress in this area, including advances using “neurofilament light chain” as a biomarker. (Such as Abstracts #183, #249) These early results need further development but indicate that  sensitive biomarkers for predicting disease course and response to therapy may become useful tools for the clinical management of MS.

RESTORING FUNCTION – WELLNESS, LIFESTYLE, SYMPTOMS

Home-based rehabilitation can work: With funding from the National MS Society, Dr. Gabriel Pardo (Oklahoma Medical Research Foundation) and colleagues compared the benefits of three approaches to rehabilitation for gait and balance in a small study: unsupervised home-based exercise 5 times/week; home-based exercise supervised remotely by a physical therapist 2-3 times per week via audio and visual conferencing; and home-based exercise plus in-person physical therapy 2-3 times/week. They found that all participants improved, and that the telerehabilitation program worked as well as the onsite program to improve gait and balance. Further research in larger trials could make telerehabilitation a cost-effective and more accessible alternative for people with MS. (Abstract #120)

Tackling fatigue: Dr. Vincent de Groot (VU University Medical Center, Amsterdam) reported results from three clinical trials testing different strategies over 16 weeks to lessen fatigue, in 90 people with MS: aerobic training, cognitive behavioral therapy, and energy conservation management. Only cognitive behavioral therapy effectively reduced severe fatigue in this short-term study. This is a commonly available type of psychotherapy. (Abstract #142) Read more about managing fatigue

Pain more common than previously reported: Dr. Carolyn Young (University of Liverpool) and colleagues found that nearly 66% of over 700 people with MS reported nerve pain. Higher levels were found in those who had MS for a longer time, had more severe disability, or were not working. (Abstract #P337Read more about addressing pain in MS

New trial confirms Ampyra (fampridine) benefits: Dr. Jeremy Hobart (Plymouth Hospitals NHS Trust) presented results from a large clinical trial of fampridine, a twice-a-day oral therapy that was previously approved for its ability to improve walking.. This trial wanted to show evidence that its benefits include meaningful functional improvements for people. The results over 6 months showed that 43% of those on active therapy had significantly better self-reported walking ability, mobility, and balance than those on placebo, with no new safety issues reported. (Abstract #254)

Cognitive rehabilitation enhances brain connections: Several studies showed that rehabilitation to improve cognition goes hand-in-hand with changes in brain connectivity (how areas of the brain interact). While many of these treatments are still experimental, some are available from rehabilitation specialists such as speech pathologists or neuropsychologists. Discuss options with your MS doctor:

  • Dr. Brian Sandroff (Kessler Foundation, West Orange, NJ) and colleagues showed that treadmill training improved information processing speed and brain connectivity in a small pilot study funded by the Society. (Abstract #P796)
  • Dr. Pietro Iaffaldano (University of Bari, Italy) and colleagues showed that a home-based computerized training program that targeted specific cognitive issues improved overall cognitive function significantly more than a non-specific program. Also, those who had less function in certain brain areas showed greater improvement after cognitive training. (Abstract #145)
  • Oiane Rilo (University of Deusto, Bilbao, Spain) and colleagues showed that a three-month, group-based cognitive rehabilitation program improved working memory, information processing speed, verbal memory and executive function (which is important in problem solving and planning), and altered brain connectivity. (Abstract #144)

Emerging treatment for muscle spasticity: Dr. Daniel Kantor (Kantor Neurology, Ponte Vedra Beach, FL) and colleagues report that in a trial of 354 people with relapsing-remitting or secondary progressive MS, Arbaclofen Extended Release Tablets (Osmotica Pharmaceuticals) significantly reduced spasticity compared to baclofen. The extended-release tablets caused significantly less sleepiness, drowsiness and dizziness than baclofen. (Abstract #128) The company reports that it has filed for FDA approval of Arbaclofen.

RESTORING FUNCTION – NERVOUS SYSTEM REPAIR

More Anti-LINGO Results: In June 2016 Biogen announced that its phase 2 clinical trial of anti-LINGO (proposed name opicinumab), an approach to repair myelin, did not meet its primary endpoint of improvement in physical function, cognitive function, or disability. The trial involved 418 people with relapsing MS who were taking interferon beta-1a (Avonex) plus one of several doses of intravenous opicinumab or placebo for 72 weeks. Dr. Diego Cadavid from the company described ongoing evaluations from the extensive testing and monitoring during the trial, which are helping to pinpoint the patient population, dosage and outcome measures that would inform the design of any future trials of anti-LINGO.  (Abstract #192)

Myelin repair in pediatric and adult MS: Dr. Sabine Pfeifenbring (University of Göttingen, Germany) and an international team analyzed brain biopsies from children who had been diagnosed with MS and compared the extent of damage and natural myelin repair against those of adults with MS. They found that children showed less damage to myelin-making cells and more evidence of myelin repair than adults. However, some myelin repair was found to occur at virtually all ages in MS. (Abstract #194)

Exercise enhances myelin repair in mice: To investigate some reasons why exercise promotes benefits in people with MS, Drs. S. Jensen and Wee Yong (University of Calgary) did a study where mice with myelin damage in their spinal cords used running wheels soon after the injury. They reported finding more evidence of generation of myelin-making cells and myelin repair in the active mice than those that did not use the running wheels after injury. (Abstract: #P1210)

Emerging approaches to protection and repair:  Dr. Martin Sanders (Io therapeutics) presented results from mice suggesting that the compound IRX4204 promotes repair of damaged myelin in mice. He noted that previous studies suggested that IRX4204 also showed signs of reducing immune attacks and protecting against nerve loss. This work was supported in part by a National MS Society’s Fast Forward investment. (Abstract #193)

Drs. Sarah Starossom, Samia Khoury and team (Brigham and Women’s Hospital, Boston) reported on studies of Chi3l3, a naturally occurring molecule in the brain that can stimulate the transformation of resident stem cells into myelin-making cells. The team noted that it plays an important role in recovery from the MS-like disease in mice, and may have potential for development as a new treatment approach in MS. (Abstract #195)

Positive Results Announced from Clinical Trial of BAF-312 (Siponimod) in Secondary Progressive MS

Summary

Results presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) provided additional details from a 60-month, phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS.

The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced lesion volume.

The therapy was generally well tolerated and similar to adverse events reported for similar compounds.

Details

Background: Siponimod (BAF312) is an experimental immune system-modulating therapy that was designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya® (fingolimod, Novartis International AG). Gilenya, was approved in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug;12(8):756-67).  Siponimod is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Siponimod also distributes effectively to the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects.

The Study: Participants were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale at three months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months versus placebo, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/ tolerability.

Results:  Results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on September 17, 2016. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had at 26% reduced risk of disability progression (confirmed at 6 months), a 23.4% lower average change in brain volume, and reduced MRI-detected brain lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

Safety: The therapy was generally well tolerated and similar to adverse events reported for similar compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.

Comment:
“These results suggest a modest benefit for people with secondary progressive MS, which is a positive step forward in the global effort to speed solutions for people living with this chronic form of the disease,” said Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer at the National MS Society. “We look forward to learning additional details about its potential benefit and safety.”

MS Trial Alert: Researchers Recruiting People with Relapsing MS for Antibody Study

Summary: Investigators at seven sites in the United States are recruiting at least 24 people with relapsing MS for a study of ublituximab (TG Therapeutics, Inc.), an experimental monoclonal antibody administered via intravenous infusion. At most, 100 people will be enrolled.

Rationale: Ublituximab is a new monoclonal antibody that binds to a molecule (CD20) on the surface of immune cells called B cells, and depletes them from circulation. B cells have several functions including making antibodies, and evidence suggests they play a role in immune-system mediated damage to brain and spinal cord tissues in MS. Other therapies targeting B cells (rituximab, ocrelizumab) have shown some benefit in clinical trials. Ublituximab binds to CD20 in a unique way, and thus may have greater B cell depletion capabilities than similar agents. Clinical trials are ongoing in people with blood cancer as well.

Eligibility and Details: Participants should be aged 18 to 55, have a diagnosis of relapsing MS, and have had more than one relapse in the previous two years. Further enrollment criteria are available from the contact below.

Participants are initially randomly assigned to receive either ublituximab or placebo infusions (infusions range from 1 to 4 hours).  After 28 days, participants receiving placebo will receive ublituximab.

The primary outcomes being measured are the levels of B cell depletion, and the number of participants who experience adverse events. Secondary outcomes include monitoring relapses and MRI-detected disease activity.

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact Koby Mok, PhD, via e-mail at kmok@tgtxinc.com, or by phone at 949-422-2468.

Sites are enrolling in the following cities:
Fort Collins, CO
Lexington, KY
San Antonio, TX
Knoxville, TN
Columbus, OH
Phoenix, AZ
Round Rock, TX

Download a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF).

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