Wednesday, May 14

FREE MS RESEARCH UPDATE: a comprehensive overview of research findings on all of the FDA-approved disease-modifying therapies, as well as many experimental treatments

This year's expanded MS Research Update incorporates new information about the approved disease-modifying therapies (DMTs), as well as numerous experimental drugs currently under investigation for the long-term treatment of multiple sclerosis (MS). Highlights and recent research results are provided for each drug. Please note that symptom-management drugs are not included in this report.

 This information is based on a wide range of sources, including the
 extensive  journal literature on MS and its management, a review of ongoing
 clinical trials, and papers presented at major national and international
 conferences. These include the 2013 conferences hosted by the American Academy of Neurology (AAN), the Consortium of Multiple Sclerosis Centers (CMSC), and the American and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS and ECTRIMS).

This 2014 edition of MSAA's MS Research Update is being printed as a stand-alone issue, reflecting the incredible diversity and scope of research progress in MS. There is nonetheless far too much ongoing research in MS therapeutics for all of it to be covered here. This is therefore not a complete list, and not all study results could be included.

Stephen Krieger, MD
The year 2013 marked the 20th anniversary of the United States Food and Drug Administration's (FDA) approval of Betaseron®, the first disease-modifying therapy for MS, and the beginning of the MS-treatment era. This medicine, and other available medications that followed, continue to show effectiveness over the long term. Importantly, these medications have also demonstrated a proven long-term safety track record, which is crucial when considering that people with MS often require treatment for decades.

A recent review by Mark S. Freedman, MD, in the journal Neurology1, summarized the positive long-term data for Avonex®, Betaseron®, Extavia®, Rebif®, and Copaxone®. These are the five FDA-approved drugs given via self-injection for the long-term treatment of MS. All five drugs (given individually, not in combination) reduce the frequency and severity of relapses. They also show that long-term treatment improves outcomes by delaying the time to significant disease progression. In addition, treatment begun early in the disease process is correlated with optimal outcomes over the long term.

Female doctorPreferably, treatment is now often started when a person is diagnosed as having a clinically isolated syndrome (CIS). This is defined as a single attack (or the appearance of one or more symptoms characteristic of MS), with a very high risk of developing MS, when no other diseases or causes for symptoms are apparent. The use of MRI scans to identify lesions characteristic of MS has taken away the need to watch and wait for a second attack of MS in order to make this diagnosis. Numerous studies with multiple types of disease-modifying therapies (DMTs) have confirmed that early treatment at the time of CIS is beneficial in the long term.

Tysabri® is another important DMT option available for individuals with MS. Given via intravenous (IV) infusion, Tysabri is effective in reducing MS-disease activity, both in terms of relapses and lesions as seen on MRI scans. However, this medication does carry a small risk of a viral brain infection called PML (described on page 12), caused by the JC virus. A blood test to identify those who have been exposed to the JC virus, along with the recognition of other risk factors, allows clinicians to minimize this risk.

Three oral medications have been approved to treat MS in the past three years. In September 2010, Gilenya® (fingolimod) became the first oral DMT approved by the FDA for the treatment of relapsing forms of MS. Studies show that it reduces disease activity and the progression of disability, while offering the advantages of an oral medication to individuals who have difficulty with the injected DMTs. Particularly when starting this treatment, and at regular intervals afterwards, patients are monitored for potential adverse events.

September 2012 saw the FDA approval of the second oral DMT for relapsing forms of MS, Aubagio® (teriflunomide). As with all of the approved drugs for MS, information on this medication's clinical trial results, efficacy, and safety will be discussed in the pages to follow. Aubagio uses an entirely different mechanism of action, and presents another oral option to treat relapsing forms of MS.

The FDA approved the third oral DMT in March 2013, called Tecfidera™ (dimethyl fumarate or DMF; formerly known as BG-12). The data leading to its approval for relapsing MS, as well as ongoing studies, are included in this update. As MSAA Chief Medical Officer Dr. Jack Burks explains, "With the FDA approval of Tecfidera, a pill taken twice daily, another first-line oral treatment option for people with relapsing forms of MS becomes available. The combination of robust effectiveness data with only transient side effects (consisting mainly of flushing and gastrointestinal symptoms) adds a valuable treatment to the list of options for patients and doctors to discuss."

Another new medication given by infusion, Lemtrada® (alemtuzumab, formerly known as Campath), was initially denied FDA approval in December, 2013. The pharmaceutical company Genzyme plans to appeal this decision. Please see details on these and many other new and emerging therapies in the pages to follow. As therapies for progressive forms of MS remain a crucial unmet need, this Research Update highlights in bold those clinical trials that include or focus on primary- and secondary-progressive MS.