Siponimod

Siponimod, sold under the brand name Mayzent, is a selective sphingosine-1-phosphate receptor modulator for oral use that is used for multiple sclerosis (MS).[8] It is intended for once-daily oral administration.[9][8]

Siponimod
Clinical data
Trade namesMayzent[1]
Other namesBAF-312
AHFS/Drugs.comMonograph
MedlinePlusa619027
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • 1-({4-[(1E)-1-({[4-Cyclohexyl- 3-(trifluoromethyl)phenyl]methoxy}imino)ethyl]-2-ethylphenyl}methyl)azetidine-3-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC29H35F3N2O3
Molar mass516.605 g·mol−1
3D model (JSmol)
  • CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
  • InChI=1S/C29H35F3N2O3/c1-3-21-14-23(10-11-24(21)15-34-16-25(17-34)28(35)36)19(2)33-37-18-20-9-12-26(22-7-5-4-6-8-22)27(13-20)29(30,31)32/h9-14,22,25H,3-8,15-18H2,1-2H3,(H,35,36)/b33-19+
  • Key:KIHYPELVXPAIDH-HNSNBQBZSA-N

In March 2019, it was approved in the United States to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.[1]

Medical uses

Siponimod is indicated for the treatment of secondary progressive multiple sclerosis (SPMS), which is the progressive neurological decline of multiple sclerosis that happens independent of acute relapses.[1] In active SPMS, siponimod decreases the risk of disability and MS relapses.[1]

Adverse effects

In clinical trials of siponimod, the most common adverse effects were headache, high blood pressure, and liver function test abnormalities.[1]

Pharmacology

Mechanism of action

Siponimod binds selectively to some of the sphingosine-1-phosphate receptor forms—including sphingosine-1-phosphate receptor 1—found on lymphocytes and other cell types.[10]

This binding inhibits the migration of the lymphocytes to the location of the inflammation (e.g. in MS).

Siponimod may be very similar to fingolimod but preventing lymphopenia, one of its main side effects, by preventing egress of lymphocytes from lymph nodes. Siponimod may be more selective in the particular sphingosine-1-phosphate receptors (five in number) that it modulates.[11] It is selective for the -1 and -5 SIP receptors.[9]

History

In March 2019, siponimod was approved in the United States to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.[1][12][13]

The efficacy of siponimod was shown in a clinical trial[14] of 1,651 patients that compared siponimod to placebo in people with secondary progressive multiple sclerosis (SPMS) who had evidence of disability progression in the prior two years and no relapses in the three months prior to enrollment.[1][12] The primary endpoint of the study was the time to three-month confirmed progression in disability.[1] The trial was conducted at 294 centers in Asia, Australia, Canada, Europe, South America, and the United States.[12]

The U.S. Food and Drug Administration (FDA) granted approval of Mayzent to Novartis.[1][12]

Siponimod was approved for medical use in Australia in October 2019.[2]

In January 2020, siponimod was approved in the European Union for the treatment of adults with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity.[15][7]

References
  1. "FDA approves new oral drug to treat multiple sclerosis". U.S. Food and Drug Administration (FDA) (Press release). 26 March 2019. Archived from the original on 27 November 2019. Retrieved 24 November 2019.Public Domain This article incorporates text from this source, which is in the public domain.
  2. "Mayzent Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 13 December 2019. Retrieved 23 August 2020.
  3. "Summary for ARTG Entry:310499 Mayzent siponimod 2 mg film-coated tablet blister pack" (PDF). Therapeutic Goods Administration (TGA). Retrieved 23 August 2020.
  4. "Mayzent Product information". Health Canada. Retrieved 29 May 2022.
  5. "Summary Basis of Decision (SBD) for Mayzent". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  6. "Mayzent 2 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 24 April 2020. Retrieved 23 August 2020.
  7. "Mayzent EPAR". European Medicines Agency (EMA). 12 November 2019. Retrieved 3 May 2020.
  8. "Mayzent- siponimod tablet, film coated". DailyMed. 26 March 2019. Retrieved 22 January 2020.
  9. Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E (2014). "Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial". Multiple Sclerosis and Related Disorders. 3 (6): 752. doi:10.1016/j.msard.2014.09.185. ISSN 2211-0348.
  10. Gergely, P., Nuesslein-Hildesheim, B., Guerini, D., Brinkmann, V., Traebert, M., Bruns, C., Pan, S., Gray, N. S., Hinterding, K., Cooke, N. G., Groenewegen, A., Vitaliti, A., Sing, T., Luttringer, O., Yang, J., Gardin, A., Wang, N., Crumb, W. J., Jr, Saltzman, M., Rosenberg, M., … Wallström, E. (2012). The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. British journal of pharmacology, 167(5), 1035–1047. https://doi.org/10.1111/j.1476-5381.2012.02061.x
  11. WO 2008000419, Hiestand, Peter C & Schnell, Christian, "S1P Receptor modulators for treating multiple sclerosis", published 2008-01-03, assigned to Novartis
  12. "Drug Trials Snapshots: Mayzent". U.S. Food and Drug Administration (FDA). 19 April 2019. Archived from the original on 28 September 2019. Retrieved 24 November 2019.Public Domain This article incorporates text from this source, which is in the public domain.
  13. "Drug Approval Package: Mayzent (siponimod)". U.S. Food and Drug Administration (FDA). 3 May 2019. Retrieved 22 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  14. Clinical trial number NCT01665144 for "Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)" at ClinicalTrials.gov
  15. "Novartis announces EU approval of Mayzent (siponimod) for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease". Novartis (Press release). 20 January 2020. Retrieved 23 January 2020.

Further reading
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