Clinical Pearls on Siponimod
In this episode, Adnan Subei, DO, FAAN, discusses siponimod, a selective S1P receptor modulator approved in 2019, its clinical advantages, efficacy, and how it may be useful for patients with multiple sclerosis.
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
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, discussed how siponimod, the second approved S1P receptor modulator, differs from fingolimod, the therapy that came before it. He highlighted siponimod’s advantages in reducing side effects like cardiac issues and macular edema. In addition, he also explained its efficacy in treating secondary progressive MS, particularly in active cases, and mentions the importance of genetic testing to determine proper dosing.
Transcript edited for clarity.
Adnan Subei, DO: Siponimod, approved in 2019, represents a shift towards more selective S1P receptor modulators with targeted lymphocyte sequestration and potential CNS action, while minimizing side effects like cardiac issues and macular edema seen with earlier therapies like fingolimod. Siponimod specifically targets S1P1 and S1P5 receptors, with S1P5 present on CNS oligodendrocytes, suggesting potential brain penetration and impact. Its approval stemmed from the EXPAND trial, which uniquely included both active and non-active secondary progressive MS patients, demonstrating a 21% reduction in disability worsening. Despite some debate over trial design and its effect on the degenerative aspects of MS, siponimod is widely used in clinical practice, though genetic testing for the CYP2C9 gene is required to determine appropriate dosing.
