Siponimod Explained

Width:275
Tradename:Mayzent
Dailymedid:Siponimod
Pregnancy Au:D
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth
Atc Prefix:L04
Atc Suffix:AE03
Legal Au:S4
Legal Au Comment:[2] [3]
Legal Ca:Rx-only
Legal Ca Comment:[4] [5]
Legal Uk:POM
Legal Uk Comment:[6]
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Status:Rx-only
Index2 Label:as salt
Cas Number:1230487-00-9
Pubchem:44599207
Drugbank:DB12371
Chemspiderid:29315058
Unii:RR6P8L282I
Kegg:D11460
Kegg2:D11072
Chembl:2336071
Synonyms:BAF-312
Iupac Name:1-(methyl)azetidine-3-carboxylic acid
C:29
H:35
F:3
N:2
O:3
Smiles:CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
Stdinchi: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+
Stdinchikey:KIHYPELVXPAIDH-HNSNBQBZSA-N

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).[7] It is intended for once-daily oral administration.[8]

In March 2019, it was approved in the United States to treat adults with relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.[9]

Medical uses

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

Adverse effects

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

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]

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.[8]

History

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

The efficacy of siponimod was shown in a clinical trial of 1,651 patients that compared siponimod to placebo in people with secondary progressive multiple sclerosis who had evidence of disability progression in the prior two years and no relapses in the three months prior to enrollment.[13] The primary endpoint of the study was the time to three-month confirmed progression in disability. The trial was conducted at 294 centers in Asia, Australia, Canada, Europe, South America, and the United States.

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

Siponimod was approved for medical use in Australia in October 2019.

In January 2020, siponimod was approved in the European Union for the treatment of adults with secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity.[14] [15]

Notes and References

  1. Web site: Mayzent Australian prescription medicine decision summary . Therapeutic Goods Administration (TGA) . 13 December 2019 . 23 August 2020.
  2. Web site: Summary for ARTG Entry:310499 Mayzent siponimod 2 mg film-coated tablet blister pack . Therapeutic Goods Administration (TGA) . PDF . 23 August 2020 .
  3. Web site: Australian Public Assessment Report for Siponimod . Therapeutic Goods Administration (TGA) .
  4. Web site: Mayzent Product information . Health Canada . 29 May 2022.
  5. Web site: Summary Basis of Decision (SBD) for Mayzent . Health Canada . 23 October 2014 . 29 May 2022.
  6. Web site: Mayzent 2 mg film-coated tablets - Summary of Product Characteristics (SmPC) . (emc) . 24 April 2020 . 23 August 2020.
  7. Web site: Mayzent- siponimod tablet, film coated . DailyMed . 26 March 2019 . 22 January 2020.
  8. Kappos L, Bar-Or A, Cree B, Fox R, Giovannoni G, Gold R, Vermersch P, Lam E, Pohlmann H, Wallström E . Siponimod (BAF312) for the treatment of secondary progressive multiple sclerosis: Design of the phase 3 EXPAND trial . Multiple Sclerosis and Related Disorders . 3 . 6 . 2014 . 2211-0348 . 10.1016/j.msard.2014.09.185 . 752.
  9. FDA approves new oral drug to treat multiple sclerosis . U.S. Food and Drug Administration (FDA) . 26 March 2019 . https://web.archive.org/web/20191127022957/https://www.fda.gov/news-events/press-announcements/fda-approves-new-oral-drug-treat-multiple-sclerosis . 27 November 2019 . live . 24 November 2019.
  10. Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, Groenewegen A, Vitaliti A, Sing T, Luttringer O, Yang J, Gardin A, Wang N, Crumb WJ, Saltzman M, Rosenberg M, Wallström E . 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 . 1035–47 . November 2012 . 22646698 . 3485666 . 10.1111/j.1476-5381.2012.02061.x .
  11. WO. 2008000419. S1P Receptor modulators for treating multiple sclerosis . Peter C. Hiestand . Christian. Schnell . Novartis. 2008-01-03.
  12. Web site: Drug Approval Package: Mayzent (siponimod) . U.S. Food and Drug Administration (FDA) . 3 May 2019 . 22 January 2020.
  13. Web site: Drug Trials Snapshots: Mayzent . U.S. Food and Drug Administration (FDA) . 19 April 2019 . https://web.archive.org/web/20190928001701/https://www.fda.gov/drugs/drug-safety-and-availability/drug-trials-snapshots-mayzent . 28 September 2019 . live . 24 November 2019 .
  14. Novartis announces EU approval of Mayzent (siponimod) for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease . Novartis . 23 January 2020 . 20 January 2020.
  15. Web site: Mayzent EPAR . European Medicines Agency (EMA) . 12 November 2019 . 3 May 2020.