Effectiveness and Advantages of Ozanimod

EP: 1.Overviewing Mechanism of Action of S1P-Modulating Treatments

EP: 2.Setting the Stage of S1Ps With Fingolimod

EP: 3.Clinical Pearls on Siponimod

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EP: 4.Effectiveness and Advantages of Ozanimod

EP: 5.Ponesimod and the Future Questions About S1P Modulator Use

EP: 6.Future Directions and Unanswered Questions Regarding S1P Modulator Receptors

Over the years, the multiple sclerosis (MS) neurotherapeutic landscape has rapidly evolved, with new disease-modifying treatments of various novel mechanisms that have improved efficacy and safety. It has been thought that a more tailored approach to treatment will allow for better personalization of drug selection for patients. Sphingosine 1-phosphate (S1P) receptor modulators, one of the newer drug classes, have emerged as a disease-modifying option for MS that has a unique mechanism of action compared with other therapies.

To date, 4 S1P receptor modulators: fingolimod (Gilenya; Novartis), ozanimod (Zeposia; BMS), ponesimod (Ponvory; Janssen), and Siponimod (Mayzent; Novartis), are approved by the FDA and the European Medicines Agency for the treatment of MS. Fingolimod, a nonselective S1P receptor modulator targeting S1P1, S1P3, S1P4, and S1P5, was the first approved therapy in this class, dating back to 2010. This class of medications function by blocking the lymphocytes to egress from lymph notes, leading to a reduction in the number of lymphocytes in the peripheral blood.

As part of a new series, neurologists Patricia Coyle, MD, FAAN, and Adnan Subei, DO, cover the ins and outs of S1P-modulating treatments and their role in the clinical management of MS. The duo give background on how each treatment differs and the advantages each possess, as well as how clinicians have optimized these treatments as experience with them grows.

In this segment, Subei, medical director for the Multiple Sclerosis Program at Neurology Consultants of Dallas, provided clinical insight on ozanimod, the third approved S1P receptor modulator for MS. He highlighted its superior efficacy in reducing relapse rates and brain volume loss compared with interferon-beta-1a, based on the Sunbeam and Radiance trials. He also mentions the continued effectiveness observed in the Daybreak extension trial, emphasizing ozanimod’s ability to penetrate the central nervous system and positively impact cognitive function.

Transcript edited for clarity.

Adnan Subei, DO: Ozanimod is another selective S1P receptor modulator, specifically targeting S1P1 and S1P5 receptors. Its effectiveness was demonstrated in the Sunbeam and Radiance trials, where it was compared against interferon beta-1a and showed superior efficacy, with about a 40-45% reduction in annualized relapse rates. Additionally, the trials revealed significant benefits in reducing MRI activity, including T2 lesions and gadolinium-enhancing lesions, as well as brain volume loss, particularly in the thalamus and cortex. The Daybreak open-label extension trial further confirmed the sustained efficacy of ozanimod in relapse rate reduction and MRI activity, along with positive cognitive effects, emphasizing its selectivity and CNS penetration.