Siponimod

Siponimod
Names
Trade namesMayzent[1]
Other namesBAF-312
IUPAC name
  • 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]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
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)
    SMILES
    • CCC1=C(C=CC(=C1)C(=NOCC2=CC(=C(C=C2)C3CCCCC3)C(F)(F)F)C)CN4CC(C4)C(=O)O
    InChI
    • 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 2 3 4 5 6 7 8 "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. 1 2 3 4 5 6 "Mayzent". Archived from the original on 27 March 2020. Retrieved 12 October 2021.
    3. 1 2 3 4 5 6 "Mayzent- siponimod tablet, film coated". DailyMed. 26 March 2019. Archived from the original on 29 August 2021. Retrieved 22 January 2020.
    4. 1 2 "Mayzent Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 13 December 2019. Archived from the original on 5 March 2020. Retrieved 23 August 2020.
    5. ↑ "Siponimod (Mayzent) Use During Pregnancy". Drugs.com. 15 April 2019. Archived from the original on 29 November 2020. 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.{{cite web}}: CS1 maint: url-status (link)
    7. ↑ "Mayzent 2 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 24 April 2020. Archived from the original on 2 March 2021. Retrieved 23 August 2020.
    8. 1 2 "Mayzent EPAR". European Medicines Agency (EMA). 12 November 2019. Archived from the original on 27 March 2020. Retrieved 3 May 2020.
    9. 1 2 3 "Siponimod Monograph for Professionals". Drugs.com. Archived from the original on 25 February 2021. Retrieved 12 October 2021.
    10. ↑ "Mayzent Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 26 February 2021. Retrieved 12 October 2021.
    11. ↑ BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – 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 
    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. 1 2 3 4 "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. Archived from the original on 25 November 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. Archived from the original on 30 April 2020. Retrieved 23 January 2020.
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