Promising Emerging Therapies Reported at MSPARIS2017

It’s been a real energy boost to attend this conference and to feel the buzz of 10,000 people talking about the latest groundbreaking MS research. The topic of emerging therapies is near and dear to me, since I work on the research team that sniffs out possible new approaches to treating MS and restoring function.
One of these is the first report from the trial of ibudilast in people with primary progressive or secondary progressive MS. This is an oral compound that has been used in Japan at a lower dose to treat asthma and post-stroke dizziness. It’s being tested to see if it can protect the nervous system from MS damage. In a phase 2 trial involving 255 people, ibudilast was found to slow the rate of brain atrophy (shrinkage) by 48% compared to a placebo. Finding a way to slow brain atrophy, which has been linked to cognitive and physical disability in MS, may significantly slow disease progression. The main side effects were nausea and skin rash.
Before this can go to the FDA for approval, one or more larger trials will likely be needed so that its potential benefits and risks can be further outlined. But it’s a terrific first step! (Abstract 278)
In the largest clinical trial yet in children and adolescents with MS, oral fingolimod (Gilenya) reduced the annual number of relapses by 82% over two years, compared to treatment with Avonex. After two years, 86% of those on fingolimod had not experienced a relapse, compared to 39% of the Avonex group. The trial also showed benefits measured by MRI. Side effects were similar to what have been seen in the adult population. This therapy isn’t currently approved for the treatment of pediatric MS, but the company, Novartis, has announced plans to analyze these data and present the results to regulatory authorities. (Abstract 276)
There are several other therapies being developed that are similar to fingolimod. Fingolimod is called a “sphingosine 1-phosphate” (S1P) receptor modulator, which is thought to act by retaining certain white blood cells in the lymph nodes, preventing these cells from entering the central nervous system to reduce inflammatory damage to nerve cells.
Several therapies are under development to be more selective S1P receptor modulators in hopes of reducing side effects. One is called siponimod. It was previously announced that siponimod could slow the progression of disability in secondary progressive MS. This week we heard additional promising imaging data from the phase 3 trial, indicating siponimod reduced MRI-detected disease activity and brain atrophy, which was detected as early as week 12. (Abstract 129)
Yet another S1P receptor modulator called ozanimod has recently completed two phase 3 clinical trials for relapsing MS. This week the investigators shared results from both trials called “SUNBEAM” and “RADIANCE.” Both trials suggested that ozanimod significantly reduced relapse rates compared to people on Avonex over two years and showed benefits against MRI-detected disease activity. Although there was no evidence that ozanimod slowed the progression of disability compared to those on Avonex, both groups had low progression so it would be difficult to see an effect. (Abstracts 232, 280)
This spring, the FDA approved Ocrevus, which depletes immune B cells, for the treatment of primary progressive and relapsing forms of MS. Researchers are now working on ways to quiet B cells rather than depleting them in hopes of rebalancing the immune system. There’s been progress in this approach in mouse models of MS, and there is even a phase 2 trial getting underway of an experimental oral therapy called (here’s a mouthful) “evobrutinib.” This is a small molecule that inhibits an enzyme in B cells called Bruton’s tyrosine kinase (Abstract P675). I think we may hear more about this approach in the near future.
There were also several presentations related to emerging approaches to repairing the nervous system. I’m going to refer you to my colleague Doug Landsman’s blog for more info. And I highly recommend Kathleen Zackowski’s blog on wellness advances reported at MSParis2017.
If you’d like to learn more, the content of the meeting is online. To find content and keep up with news, visit our web hub for MSPARIS2017.
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Walt Kostich

Dr. Walt Kostich is the director of commercial research at the National MS Society, managing commercial research partnerships developed through Fast Forward. He also supports the Society’s portfolio of biomedical research grants. A neuroscientist by training, Walt joined the Society in 2015 following a 20-year career in the pharmaceutical industry in neuroscience drug discovery.