From 1 November 2020, siponimod became available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of relapsing-remitting multiple sclerosis. Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. It acts as a functional antagonist at S1P1 receptors to inhibit the release of lymphocytes from the lymph nodes. This may reduce lymphocyte migration to the central nervous system and minimise central inflammation.
A large double-blind clinical trial demonstrates that siponimod reduces disability progression and has a similar safety profile to fingolimod. The primary endpoint of time to onset of confirmed disability progression (CDP) at three months was significantly delayed, with a relative risk reduction of 21% (CDP events occurred in 26% of siponimod patients, compared to 32% of the placebo group). Adverse events most commonly reported during this trial include elevated liver enzymes, bradycardia at initiation, macular oedema, hypertension, varicella-zoster virus reactivation, and convulsions.
Siponimod is extensively metabolised by the cytochrome P450 system, primarily by CYP2C9. Patients should be tested for their CYP2C9 metabolising enzyme status before commencing treatment. Dose reductions are required for patients with CYP2C9*1*3 or CYP2C9*2*3 genotypes, while use is contraindicated in patients with a CYP2C9*3*3 genotype as substantially higher plasma levels will occur.
- Australian Government Department of Health. Australian Public Assessment Report for Siponimod. Woden: TGA; 2019.
- Kappos L, Bar-Or A, Cree BA, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018; 391(10127): 1263-73.
- Mayzent® (Siponimod) Australian approved product information. Macquarie Park: Novartis Pharmaceuticals. Approved November 2019.