An Overview of the Efficacy and Safety of Ozanimod for the Treatment of Relapsing Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a complex disease of the central nervous system that can cause permanent disability in young adults. A large armamentarium is available for its management and is increasing over time. Ozanimod is an oral drug belonging to the sphingosine-1-phosphate receptor (S1PR) modulator family recently approved in different countries for MS with active disease. It selectively modulates S1PR1 and S1PR5 to prevent autoreactive lymphocytes from entering the central nervous system (CNS), where they can determine inflammation and neurodegeneration. Ozanimod was tested in one Phase II and two Phase III pivotal trials and was shown to be effective and well tolerated. Moreover, further investigations, including comparative trials with other S1P modulators and MS disease-modifying drugs, are needed to better define placement in MS treatment. Furthermore, ozanimod is currently under evaluation for inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, in international phase III studies. This article retraces the itinerary leading to the approval of ozanimod for MS treatment and its peculiarities and potentiality inside the S1PR modulator family.

Selective Forms of Therapy in the Treatment of Inflammatory Bowel Diseases

“…They are found on many cells of the body, but the S1P1 and S1P5 isoforms are present mainly in immune system cells and they are the center of action of ozanimod, which limits the effect of the drug on other organs [22]. According to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), treatment with ozanimod is currently approved in adult patients with relapsing-remitting MS [23]. The TOUCHSTON, a phase 2 placebo-controlled trial and the True North, a phase 3 placebo-controlled trial, and Phase II and III studies have shown efficacy in remission induction and maintenance therapy in adults with moderate to severe UC.…”

Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage

“…Fingolimod is an immune modulator that acts on S1P receptors and has been used in the treatment of Multiple Sclerosis (MS) for a decade (Chew et al, 2016). Fingolimod is non-selective and is known to modulate S1P receptors 1-5, except for S1PR2 (Fronza et al, 2021). Anecdotal evidence suggests Fingolimod's utility in SARS-CoV-2 infection, and its potential efficacy is being evaluated (Barzegar et al, 2020;Yousefi et al, 2021).…”

“…Recently, more drugs have been approved that target the S1P pathway. In 2019, the FDA approved Siponimod, an inhibitor selective for S1PR1 and S1PR5, which has shown effectiveness in MS treatment (U.S. Food and Drug Administration, 2019;Fronza et al, 2021). Ozanimod was approved for use in MS in 2020, and is selective for S1PR1 and S1PR5 as well (U.S. Food and Drug Administration, 2020; Fauzyah et al, 2021;Perez-Jeldres et al, 2021).…”

“…Ozanimod was approved for use in MS in 2020, and is selective for S1PR1 and S1PR5 as well (U.S. Food and Drug Administration, 2020; Fauzyah et al, 2021;Perez-Jeldres et al, 2021). In March 2021, Ponesimod, a highly selective inhibitor of S1PR1, was approved for patients with relapsing MS (Fronza et al, 2021;U.S. Food and Drug Administration, 2021).…”

Immunomodulatory Agents for Treatment of Patients with Inflammatory Bowel Disease (Review safety of anti-TNF, Anti-Integrin, Anti IL-12/23, JAK Inhibition, Sphingosine 1-Phosphate Receptor Modulator, Azathioprine / 6-MP and Methotrexate)

“…In summary, ozanimod is a recently approved oral medication for treatment of moderate to severe UC [61] with limited real world experience in UC, hence, most real world safety data comes from the MS patient population. Longer term and comparative efficacy and safety data are needed determine where this agent fits amongst alternative IBD therapies [63].…”