siponimod

Siponimod is an oral, selective sphingosine-1-phosphate (S1P) receptor modulator used to treat multiple sclerosis (MS). It primarily targets S1P receptors on lymphocytes, causing these cells to be retained in lymph nodes and reducing their movement into the central nervous system. This limits inflammatory activity and demyelination in MS. In many regions it is marketed as Mayzent.

Indications and efficacy: Siponimod is approved for adults with relapsing forms of MS and for secondary progressive MS with active disease. In the Phase III EXPAND trial, siponimod reduced the risk of 3-month confirmed disability progression and lowered relapse rates versus placebo in secondary progressive MS with activity, with additional improvements observed on MRI measures of disease activity. The drug’s effects are attributed to reduced CNS lymphocyte infiltration and downstream inflammatory processes.

Administration and dosing: Dosing is individualized based on CYP2C9 genotype and is titrated to the target daily dose after genotyping. A first-dose observation is commonly required due to the risk of bradycardia or other conduction disturbances. Ongoing monitoring typically includes liver function tests and periodic ophthalmologic examinations because of potential macular edema. Siponimod interacts with drugs that inhibit or induce CYP2C9, and vaccination status should be considered due to its immunomodulatory effects. Baseline assessments and contraindications related to cardiac or hepatic conditions may apply.

Adverse effects and safety: Common adverse events include headache, bradycardia after the first dose, hypertension, elevated liver enzymes, infections, and macular edema. Rare but serious risks include hepatotoxicity and infections; pregnancy should be avoided and effective contraception used during treatment and for a period after discontinuation.