Siponimod

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Siponimod
Siponimod.svg
Names
Trade namesMayzent[1]
Other namesBAF-312
  • 1-({4-[(1E)-1-({[4-Cyclohexyl- 3-(trifluoromethyl)phenyl]methoxy}imino)ethyl]-2-ethylphenyl}methyl)azetidine-3-carboxylic acid
Clinical data
Drug classSphingosine-1-phosphate receptor modulator[2]
Main usesMultiple sclerosis (MS)[3]
Side effectsHeadache, high blood pressure, liver problems[3]
Pregnancy
category
  • AU: D[4]
  • US: N (Not classified yet)[5]
Routes of
use
By mouth
Typical dose1 to 2 mg per day[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa619027
Legal
License data
Legal status
  • AU: S4 (Prescription only) [6]
  • UK: POM (Prescription only) [7]
  • US: ℞-only
  • EU: Rx-only [8]
  • In general: ℞ (Prescription only)
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

Siponimod, sold under the brand name Mayzent, is a medication used to treat multiple sclerosis (MS).[3] Specifically it is used for relapsing forms of MS including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.[3] It is taken by mouth.[3]

Common side effects include headache, high blood pressure, and liver problems.[3] Other side effects may include infection, macular edema, arrhythmias, and posterior reversible encephalopathy syndrome.[9] It should not be used in people who are allergic to peanuts or to soya.[2] It works by blocking sphingosine-1-phosphate receptors.[2]

Siponimod was approved for medical use in the United States in 2019 and Europe in 2020.[2][9] At a dose of 2 mg per day, it costs about 8,400 USD per month in the United States as of 2021.[10] In the United Kingdom this amount costs the NHS about £1,800.[11] In the United States it is only available through a specialty pharmacy.[9]

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]

Dosage

It is started at 0.25 mg once per day and increased over the first to 1 to 2 mg per day.[2]

Side effects

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.

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.[12] It is selective for the -1 and -5 SIP receptors.[13]

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][14][15]

The efficacy of siponimod was shown in a clinical trial[16] 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][14] 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.[14]

The U.S. Food and Drug Administration (FDA) granted approval of Mayzent to Novartis.[1][14]

Siponimod was approved for medical use in Australia in October 2019.[4]

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.[17][8]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "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. 2.0 2.1 2.2 2.3 2.4 2.5 "Mayzent". Retrieved 12 October 2021.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 "Mayzent- siponimod tablet, film coated". DailyMed. 26 March 2019. Retrieved 22 January 2020.
  4. 4.0 4.1 "Mayzent Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 13 December 2019. Retrieved 23 August 2020.
  5. "Siponimod (Mayzent) Use During Pregnancy". Drugs.com. 15 April 2019. Retrieved 22 January 2020.
  6. "Summary for ARTG Entry:310499 Mayzent siponimod 2 mg film-coated tablet blister pack" (PDF). Therapeutic Goods Administration (TGA). Retrieved 23 August 2020.
  7. "Mayzent 2 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 24 April 2020. Retrieved 23 August 2020.
  8. 8.0 8.1 "Mayzent EPAR". European Medicines Agency (EMA). 12 November 2019. Retrieved 3 May 2020.
  9. 9.0 9.1 9.2 "Siponimod Monograph for Professionals". Drugs.com. Retrieved 12 October 2021.
  10. "Mayzent Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 12 October 2021.
  11. BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2021 – March 2021. p. 903. ISBN 978-0-85711-369-6.
  12. WO 2008000419, Hiestand, Peter C; Schnell, Christian, "S1P Receptor modulators for treating multiple sclerosis", assigned to Novartis [non-primary source needed]
  13. 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.
  14. 14.0 14.1 14.2 14.3 "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.
  15. "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.
  16. Clinical trial number NCT01665144 for "Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)" at ClinicalTrials.gov
  17. "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.

External links

Identifiers: