MS Research Update 2019

Written and compiled by Tom Garry and Pete Kelly

Reviewed by Jack Burks, MD and Michelle Fabian, MD
Edited by Susan Courtney

The Multiple Sclerosis Association of America (MSAA) is pleased to present this 2019 edition of its MS Research Update. The Update provides important new data on approved and experimental treatments for MS, and is designed to serve as a comprehensive resource for the entire MS community. Please note that the MS Research Update focuses on research related to approved and experimental medications and therapies for the long-term treatment of multiple sclerosis. It does not include information on symptom-management medications or therapies.

For additional information about MS, symptoms and symptom management, as well as MSAA’s programs and services, please visit or call (800) 532-7667. Questions to MSAA’s Client Services department may also be emailed to

Additionally, please be aware that due to the timing of the national and international MS conferences, study data from 2019 conferences generally could not be included in the Update. Information in this publication includes data presented at the 2018 conferences, as well as any important updates that occurred in early 2019. Please visit MSAA’s website at for future summaries of 2019 conference highlights.


The 2019 MS Research Update highlights new data and findings on:

  • Experimental drugs currently under investigation for the long-term treatment of multiple sclerosis (MS)
  • FDA-approved disease-modifying therapies (DMTs)
  • New therapeutic approaches and treatment targets, such as stem-cell therapy and the gut microbiome
  • Promising areas of inquiry that are enhancing researchers’ and clinicians’ understanding of MS, such as genetics and biomarkers

This 2019 edition of MSAA’s MS Research Update is once again being printed as a stand-alone issue, reflecting the great wealth and wide scope of research progress in MS. Nonetheless, there is far too much ongoing research in MS therapeutics for all of it to be covered here. As a result, this update provides a comprehensive overview, rather than an exhaustive compilation, of relevant research; not all study results could be included. The information presented is drawn from a variety of sources, including e-journal literature on MS and its management, a review of ongoing clinical trials, and papers presented at major national and international conferences.

Please note that this MS Research Update reports on the most recent study results available at the time of publication. While every effort has been made to provide meaningful, timely, and balanced information on each medication, keeping the length of information equal for each medication is not possible. Please understand that the different lengths of text should in no way be considered as favoritism toward any one product. Additionally, references have been cited only for the newer study results.

While medications for management of MS symptoms are not within the scope of this report, information on the specific symptoms of MS and their treatment is available here.

Providing these resources is central to MSAA’s mission of being a leading resource for the entire MS community, improving lives today through vital services and support. Feedback and thoughts on the 2019 MS Research Update, as well as other MSAA publications, are welcomed. These can be directed to the organization at (800) 532-7667 or

Overview of MS Research Progress

By any measure – the United States Food and Drug Administration (FDA) approval of new medications, Phase III trials under way, expanded knowledge of the causes and course of MS, emerging treatment strategies, and many others – the last 12 months have seen great strides in the effort to better understand and more effectively manage multiple sclerosis.

The FDA’s approval of two new diseasemodifying therapies (DMTs) – just days apart – gives a sense of the pace of progress. In late March 2019, the FDA approved Novartis’ Mayzent® (siponimod) for use in adults experiencing relapsing forms of MS, including clinically isolated syndrome (CIS), relapsingremitting disease, and – notably – active secondary-progressive disease. This FDA action made Mayzent, a sphingosine 1-phosphate (S1P) receptor inhibitor, the first oral drug to treat secondary-progressive MS with active disease.1

While the DMT Novantrone® (mitoxantrone), given via IV infusion, has been approved since 2000 for reducing the neurologic disability and/or frequency of clinical relapses in adults with secondary-progressive MS, its use has been greatly limited due to its side-effect profile. Immediately following the approval of Mayzent, Mavenclad® (cladribine) was also approved for use in adults with relapsing forms of MS, including RRMS and active secondary-progressive disease. Mavenclad, which is a product of EMD Serono, is given in a two-course regimen, with the initial course separated from the second course by at least 43 weeks (about 10 months).234 Several other medications are making their way through late-stage clinical trials and the evaluation process. These include Vumerity™ (diroximel fumarate), a molecular “relative” of Biogen’s Tecfidera® (dimethyl fumarate) that Biogen and Alkermes plc are developing. This agent will offer efficacy comparable to that of Tecfidera, but with fewer of the gastrointestinal effects that sometimes are associated with Tecfidera use. The companies have filed a New Drug Application (NDA) for Vumerity, and the FDA is expected to issue a decision on that application in late 2019.5

Meanwhile, Celgene has filed an NDA with the FDA for its oral S1P receptor inhibitor ozanimod, seeking approval for use of the medication in relapsing forms of MS.6 As the MS Research Update was going to press in early May, Celgene announced that a post hoc analysis of data from its Phase III RADIANCE Part B trial showed that ozanimod reduced brain volume loss across all age groups studied in adults with relapsing MS.7 Other agents in late stages of clinical development, including the monoclonal antibodies (mAbs) ofatumumab, ublituximab, opicinumab, and temelimab, as well as the S1P receptor modulator ponesimod and other agents, all have reported research findings over the past 12 months that are summarized in this publication.

Important research also is examining the optimal use and long-term efficacy and safety profiles of medications already approved by the FDA. For example, Biogen announced in January 2019 that it had enrolled the first patients in its Phase IIIb study evaluating the impact of extending the dosing of its DMT Tysabri® (natalizumab) from every four weeks to every six weeks.8 The two-year NOVA study, which ultimately will enroll 480 patients worldwide, was initiated after smaller studies indicated that extending the dosing interval for Tysabri significantly reduced the risk of progressive multifocal leukoencephalopathy (PML) without diminishing the efficacy of the agent. Caused by the JC virus, PML is a rare but potentially life-threatening viral disease associated with the use of Tysabri and some other DMTs.

On a related note, a study published in the April 25, 2019 edition of The New England Journal of Medicine reported that Pembrolizumab, a type of cancer therapy called a PD-1 inhibitor, was given to eight individuals diagnosed with PML (all with different underlying conditions). Improved laboratory measures of PML were seen in all eight patients. Five of these eight individuals experienced clinical improvement or stabilization of their PML, along with additional improvements in laboratory measures, including a reduction in JC viral load and an increase in anti-JC viral activity.910

Two recurring themes mark much of the research into current FDA-approved DMTs. The first is that the sooner the therapy is initiated following the diagnosis of MS, the more effective the medication is likely to be. This point is highlighted in studies concerning Ocrevus® (ocrelizumab), Tysabri, and other agents, as reported in this MS Research Update.11 – 19 The second theme is that longterm studies of various DMTs demonstrate the ongoing effectiveness and consistent safety profiles of the medications, as reported in the pages that follow in summaries of research into Tecfidera, Gilenya® (fingolimod), Lemtrada® (alemtuzumab), Plegridy® (peginterferon beta- 1a), Aubagio® (teriflunomide), glatiramer acetate, Betaseron® (interferon beta-1b), and other agents.1220 – 24

As researchers are able to draw upon data encompassing several years of DMT use by thousands of people with MS, they also are able to identify patterns and trends regarding the relative impact of various agents. One important study in this regard was published in the Journal of the American Medical Association, or JAMA, in January 2019. Researchers drew on multi-year data for 1,555 patients treated at 68 neurology centers in 21 countries to examine whether initial use of particular DMTs was associated with varying degrees of risk of moving from relapsing-remitting MS to secondary-progressive MS (SPMS).

The researchers concluded that initial treatment with Gilenya, Tysabri, or Lemtrada was associated with a lower risk of conversion to SPMS compared with initial use of interferon beta or glatiramer acetate.2 “Comparative effectiveness” studies that examine how various agents perform relative to one another represents a growing area of scientific inquiry. Such studies are likely to help clinicians decide which medication is best suited to the needs of individual patients.

Of course, not all research yields positive findings. The path to progress can be a winding one with many a detour and dead end. The results of the MS-SMART trial represent a case in point. The study, sponsored by University College London, examined whether three established medications used to treat other conditions would be effective in the treatment of SPMS. The Phase II study enrolled 445 patients to receive 96 weeks of treatment with either amiloride (used to treat high blood pressure and congestive heart failure), fluoxetine (an antidepressant), riluzole (used to treat amyotrophic lateral sclerosis, also known as ALS or “Lou Gehrig’s disease”), or placebo. The primary outcome was the percentage of brain volume change as measured on MRI.3

Unfortunately, none of the medications tested slowed the brain atrophy that is a hallmark of SPMS. MS-SMART did, however, make many valuable contributions to the overall effort to improve outcomes in people with SPMS, which has posed a major challenge to clinicians for many years. The study’s innovative design showed that it is feasible to assess several agents simultaneously, an important finding as neurologists and other physicians seek treatments for many conditions that historically have lacked effective therapies. The findings also enable researchers to re-focus their efforts on other potentially fruitful avenues of inquiry.

Beyond traditional medications, exciting research findings have been reported in recent months in promising areas such as stem-cell therapy, dietary strategies, and attempts to affect MS by altering the composition of the gut microbiome – a key component of the immune system. There also is important new information on the role of genetics in MS, the significance of biomarkers such as serum neurofilament light chains and the so-called “central vein sign,” and more. Highlights from those studies also are included in this 2019 MS Research Update.

Staying current with the latest findings on the medications, techniques, and avenues of inquiry in MS is challenging, and can be daunting… not only for patients and family members, but for clinicians as well. We hope this MS Research Update will be a helpful resource for everyone working to improve the lives of people with MS.

Every study reported in this publication depended not only on the expertise of physicians, nurses, and other healthcare professionals, but also on the commitment of people with MS who made a decision to contribute to the effort to better understand, better manage, and one day conquer multiple sclerosis. If you have been part of that effort and have participated in the clinical trials or have provided assistance to MS research in some other way, you have our deepest gratitude. If you have not participated to date, we would encourage interested readers to ask their providers about possible opportunities to contribute to MS research. The more diverse populations that enroll in clinical trials, the more meaningful are the results. For more information about participating in clinical trials for the treatment of MS and its symptoms, readers may visit

Editor’s note: Initial study results for therapeutic agents under investigation should be considered as preliminary because additional studies and/or evaluations may be needed to determine the long-term safety and efficacy of these agents. MSAA does not endorse or recommend any specific products or therapies. Readers are advised to consult their physician before making any changes to their medication, diet, exercise, or other treatment regimen.

Trial Phases for Investigating Treatments

Phase I

Phase I studies are primarily concerned with assessing the drug’s safety. This initial phase of testing in humans is done in a small number of healthy volunteers, and is designed to determine what happens to the drug in the human body – how it is absorbed, metabolized, and excreted.

Phase II

Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients. Phase II studies are often “doubleblinded,” meaning that the participants, medical staff, and investigators are not told who is receiving the drug and who is receiving the placebo.

Phase III

In a Phase III study, a drug is usually tested in several hundred to several thousand patients, usually in multiple medical facilities around the world. Phase III studies typically last two or more years. Only after a Phase III study is successfully completed can a pharmaceutical company request FDA approval for marketing the drug.

Phase IV

Phase IV clinical trials are conducted after a drug has been approved. Participants are enrolled to further monitor safety and side effects, while evaluating long-term efficacy.

FDA-Approved Medications

Medications Recently Approved

March 2019 saw the United States Food and Drug Administration (FDA) approve two more medications for use in multiple sclerosis (MS) – Mayzent® (siponimod) and Mavenclad® (cladribine). Information on those agents and the clinical trial data that helped secure their approval follow.

New Data on Previously Approved Medications

Please note that not all of the approved treatments for MS have been included in this section. For a full listing, please see this chart giving an overview of the approved DMTs.

Experimental Medications

Monoclonal Antibodies

About Monoclonal Antibodies

Monoclonal antibodies are derived from cells that are identical (cloned from a single cell and then replicated). They are produced from animal tissue, most commonly laboratory mice. Humanized monoclonal antibodies are antibodies from non-human species, again commonly a mouse, whose protein sequences have been modified to increase their similarity to antibodies produced naturally in humans. Monoclonal antibodies can be extremely powerful and effective, as they can be directed specifically toward a certain segment of one of the body’s systems – such as the immune system – while leaving the other parts of the system unaffected. This can be very desirable when trying to impact a structure as complex as the immune system. The names of all monoclonal antibodies end with “mab,” including alemtuzumab (Lemtrada), ocrelizumab (Ocrevus), and natalizumab (Tysabri), which already are approved for MS. Several other monoclonal antibodies have shown promise in MS, and three of these are reviewed in this section.

New S1P Receptor Modulators

About S1P Receptor Modulators

Several investigational oral agents currently under study work in a manner similar to Gilenya® and Mayzent® in that they also trap immune cells in the lymph nodes so that they cannot get into the CNS to create lesions. Researchers recently reported new data on two of these S1P receptor modulators, ozanimod and ponesimod.

Administered Orally

New Directions in MS Research

New Therapeutic Approaches

Closing Notes

The 2019 edition of the MS Research Update is a powerful testament to the progress that has been made in understanding the potential causes of multiple sclerosis and in developing therapies to effectively treat the condition. The studies reported in this update examine everything from intricate biochemical processes occurring at the molecular level to long-term treatment outcomes in international registries with records on tens of thousands of patients. Squarely in between what can be seen with an electron microscope and what patterns can be discerned from Big Data analytics stands the ultimate focus all of this research – the individual patient.

Regardless of which questions clinical researchers and basic-science investigators set their sights on, their shared vision is to develop treatments and apply knowledge so that people with MS can live healthier, fuller, and richer lives. Recent months have seen several important advances toward that goal, as evidenced by this publication’s reports on newly approved therapies, other agents under consideration by the FDA, and still more in late stages of clinical development. Other research is better defining the role of diet and nutrition in enhancing the health of people with multiple sclerosis, while scientists also are steadily mapping the complex interactions that give rise to MS and identifying biomarkers that can speed its diagnosis and predicts its course.

In short, while MS remains a formidable foe, there never has been more cause for hope, nor more opportunity to confront and, hopefully, control multiple sclerosis – which brings us back to the individual patient. People with MS are the unsung heroes of the advances reported in this MS Research Update. Without their participation in clinical trials, without their willingness to act on the findings of those trials, and without their commitment to being proactive partners in their care, all of the efforts documented here would be for naught.

Because knowledge truly is power, staying informed of recent developments in MS is a prerequisite to taking a proactive approach. That is why MSAA is proud to provide this 2019 edition of its annual MS Research Update. We hope that you will find it of interest and value. We also hope that you will turn to MSAA throughout the year for the latest information in this exciting time of frequent, significant advances in the treatment of MS. For information about opportunities to participate in clinical trials, please visit or For more information about MS, its treatments, and MSAA’s programs and services, please contact MSAA at (800) 532-7667, or visit