57 msfocusmagazine.org The currently approved disease-modifying treatments are generallyreliable in decreasing the number of relapses in patients with multiple sclerosis; however, they have only limited efficacy in treating patients having more progressive disease courses. According to Dr. Ben Thrower, medical director of the Multiple Sclerosis Institute at Shepherd Center, “Of all of the currently approved DMTs, only ocrelizumab is approved for patients with primary-progressive multiple sclerosis. There is a clear unmet need for additional products for the treatment of patients with progressive forms of multiple sclerosis.” Several new DMTs are currently being investigated for the treatment of MS patients. Laquinimod, ozanimod, ponesimod, and siponimod all have a similar mechanism of action to fingolimod (Gilenya), as they work on the sphingosine-1-phosphate (S1P) receptor. Ofatumumab is a CD20-positive B-cell- targeting monoclonal antibody and masitinib is a mast-cell inhibitor. Phase III trial results for some of these pipeline products are expected to conclude within the next 12 months. If results are positive, manufacturers are expected to apply for U.S. Food and Drug Administration approval soon thereafter. Laquinimod is an orally-administered DMT. It is being investigated for patients with either relapsing-remitting or secondary- progressive MS. The exact mechanism of action of laquinimod is not understood. It appears that laquinimod shifts the production of “bad” T-cells to “good” T-cells. The “bad” T- cells, known asTH1 cells, are proinflammatory and cause inflammation; whereas, the “good” T-cells, known as TH2 cells, are anti- inflammatory and decrease inflammation. Previously reported phase III trials have had mixed results. In one trial, annualized relapse rates, disability progression, and the number of gadolinium-enhancing lesions were significantly improved with laquinimod compared with placebo. However, in another trial, annualized release rates were not significantly reduced with laquinimod compared with placebo. The most commonly reported adverse events in these trials were elevated liver function tests, abdominal pain, back pain, and cough. The phase III MS Pipeline By Ellen Whipple, Pharm.D. RX Update Regulating Immune Response The goal of disease-modifying treatment for MS is to regulate your immune system. Different treatments approach this complex task in different ways. Among these potential new treatments, some seek to target immune cells (T- and B-cells) directly. Others affect the immune system components (S1P and tyrosine kinase) that control how and when those cells respond.