Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of fingolimod. Ocrelizumab is a CD20-positive B-cell–targeting monoclonal antibody with a promising new mechanism of action. Ofatumumab is also a CD20 inhibitor. Daclizumab, an interleukin-2 inhibitor, has evidence of good efficacy but is associated with unfavorable side effects. Masitinib is a mast-cell inhibitor that also has shown efficacy in Alzheimer’s disease and amyotrophic lateral sclerosis. Phase 3 trials for some of these agents will conclude in the next 12 months, and their manufacturers are expected to apply for US Food and Drug Administration approval soon thereafter. This review article summarizes data for newly approved and late-phase investigational agents for the treatment of patients with MS.
A chronic disease of the central nervous system, multiple sclerosis (MS) is considered an immune-mediated disorder in which the immune system attacks healthy neuronal tissue. MS affects more than 2.3 million people worldwide. Its most common symptoms include overwhelming fatigue, visual disturbances, altered sensation, and difficulties with mobility. Symptoms vary in type and severity from patient to patient.1
Research and development in the treatment of MS has been rapid and active. For this review, the Clinical Trials.gov database was searched for phase 3 studies in MS that have been updated since December 1, 2014. “Multiple sclerosis” was the sole search term. Ninety-five results were returned, which covered approved agents being studied not only to treat patients with relapsing or progressive MS but also to address the symptoms of acute disease and its comorbidities. Moreover, the pipeline includes several new agents with different mechanisms of action. In addition to relapse prevention, an important focus of the newest classes of MS agents is to prevent disability.
This article summarizes data for the agents most recently approved for treatment of patients with MS as well as data for the key investigational agents, which, if phase 3 results continue to show promise, may prove to be significant additions to the therapeutic armamentarium.