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siponimod 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
immunomodulators, both stimulant/suppressive and stimulant	5326	1230487-00-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: siponimod siponimod fumaric acid mayzent NVP-BAF312-NX BAF-312	Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system. Molecular weight: 516.61 Formula: C29H35F3N2O3 CLOGP: 5.85 LIPINSKI: 1 HAC: 5 HDO: 1 TPSA: 62.13 ALOGS: -6.21 ROTB: 10 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

siponimod
siponimod fumaric acid
mayzent
NVP-BAF312-NX
BAF-312

Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. Siponimod binds with high affinity to S1P receptors 1 and 5. Siponimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which siponimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system.

Molecular weight: 516.61
Formula: C29H35F3N2O3
CLOGP: 5.85
LIPINSKI: 1
HAC: 5
HDO: 1
TPSA: 62.13
ALOGS: -6.21
ROTB: 10

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company
Jan. 13, 2020	EMA	Novartis Europharm Limited
March 26, 2019	FDA	NOVARTIS PHARMS CORP
June 29, 2020	PMDA	Novartis Pharma K.K.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Lymphocyte count decreased	362.89	27.20	120	4524	30137	63454241
Multiple sclerosis relapse	279.52	27.20	112	4532	48366	63436012
Lymphopenia	220.71	27.20	73	4571	18254	63466124
Gait disturbance	105.20	27.20	95	4549	183083	63301295
Multiple sclerosis	92.66	27.20	42	4602	24330	63460048
Expanded disability status scale score increased	90.50	27.20	18	4626	578	63483800
Basal cell carcinoma	75.19	27.20	38	4606	27953	63456425
Headache	73.76	27.20	150	4494	633091	62851287
Balance disorder	63.07	27.20	51	4593	84371	63400007
Dizziness	54.86	27.20	106	4538	429819	63054559
White blood cell count decreased	51.63	27.20	57	4587	139047	63345331
Heart rate decreased	50.75	27.20	35	4609	45525	63438853
Urinary tract infection	44.91	27.20	74	4570	264610	63219768
Vision blurred	43.65	27.20	43	4601	91881	63392497
COVID-19	43.08	27.20	47	4597	113056	63371322
Central nervous system lesion	42.53	27.20	19	4625	10616	63473762
Fatigue	42.15	27.20	151	4493	887877	62596501
Feeling abnormal	35.87	27.20	49	4595	148343	63336035
Secondary progressive multiple sclerosis	35.74	27.20	10	4634	1417	63482961
Product dose omission issue	33.79	27.20	61	4583	234252	63250126
Visual impairment	33.73	27.20	36	4608	84410	63399968
Hypoaesthesia	31.12	27.20	49	4595	168344	63316034
Fall	31	27.20	80	4564	392254	63092124
Optic neuritis	30.34	27.20	14	4630	8421	63475957
Paresis	30.09	27.20	10	4634	2520	63481858
Atrioventricular block first degree	29.10	27.20	13	4631	7260	63477118
Muscular weakness	28.94	27.20	40	4604	122313	63362065

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Multiple sclerosis relapse	184.75	36.35	55	1869	13078	34941929
Lymphopenia	116.94	36.35	41	1883	16294	34938713
Gait spastic	113.90	36.35	23	1901	1073	34953934
Muscle spasticity	110.95	36.35	31	1893	5857	34949150
Lymphocyte count decreased	103.93	36.35	41	1883	22581	34932426
Expanded disability status scale score increased	78.84	36.35	14	1910	323	34954684
Multiple sclerosis	68.62	36.35	22	1902	6623	34948384
Needle fatigue	65.42	36.35	14	1910	867	34954140
Relapsing-remitting multiple sclerosis	62.97	36.35	14	1910	1036	34953971
Hypertonic bladder	54.98	36.35	14	1910	1850	34953157
Basal cell carcinoma	54.73	36.35	25	1899	19633	34935374
Monoparesis	51.78	36.35	14	1910	2332	34952675
Balance disorder	50.31	36.35	30	1894	40624	34914383
Central nervous system lesion	49.16	36.35	17	1907	6446	34948561
Hypoaesthesia	48.10	36.35	34	1890	61410	34893597
Gait disturbance	44.41	36.35	37	1887	85103	34869904
Movement disorder	41.88	36.35	18	1906	12230	34942777
Micturition urgency	41.40	36.35	15	1909	6510	34948497
Dysmetria	41.35	36.35	9	1915	603	34954404
Ataxia	39.75	36.35	18	1906	13835	34941172

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Lymphocyte count decreased	302.56	31.96	109	4257	47180	79692842
Multiple sclerosis relapse	234.25	31.96	90	4276	46443	79693579
Lymphopenia	189.84	31.96	69	4297	30488	79709534
Basal cell carcinoma	145.13	31.96	60	4306	37315	79702707
Multiple sclerosis	118.79	31.96	45	4321	22237	79717785
Gait disturbance	110.44	31.96	91	4275	207415	79532607
Expanded disability status scale score increased	106.38	31.96	20	4346	641	79739381
Balance disorder	94.96	31.96	62	4304	98795	79641227
Central nervous system lesion	82.23	31.96	30	4336	13338	79726684
Urinary tract infection	61.01	31.96	75	4291	274437	79465585
Movement disorder	58.62	31.96	29	4337	27230	79712792
Relapsing-remitting multiple sclerosis	57.87	31.96	14	4352	1505	79738517
Headache	56.94	31.96	116	4250	653656	79086366
Fatigue	55.55	31.96	142	4224	929585	78810437
Needle fatigue	53.98	31.96	12	4354	890	79739132
Hypoaesthesia	53.32	31.96	57	4309	179295	79560727
Gait spastic	50.60	31.96	12	4354	1185	79738837
Hypertonic bladder	47.92	31.96	15	4351	4186	79735836
Dizziness	47.64	31.96	95	4271	526346	79213676
Muscle spasticity	46.62	31.96	23	4343	21452	79718570
Optic neuritis	46.31	31.96	18	4348	9502	79730520
Monoparesis	46.25	31.96	14	4352	3497	79736525
Heart rate decreased	41.85	31.96	33	4333	70283	79669739
Concomitant disease aggravated	40.67	31.96	18	4348	13149	79726873
COVID-19	39.76	31.96	46	4320	157628	79582394
Fall	38.21	31.96	83	4283	487546	79252476
Muscular weakness	37.39	31.96	45	4321	160684	79579338
Visual impairment	36.02	31.96	34	4332	92097	79647925
Micturition urgency	34.97	31.96	16	4350	12625	79727397
Secondary progressive multiple sclerosis	34.00	31.96	9	4357	1388	79738634
Macular oedema	32.59	31.96	12	4354	5462	79734560
Vision blurred	32.03	31.96	34	4332	105864	79634158

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L04AA42	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants
MeSH PA	D007155	Immunologic Factors
MeSH PA	D007166	Immunosuppressive Agents
MeSH PA	D000081243	Sphingosine 1 Phosphate Receptor Modulators
FDA MoA	N0000181815	Sphingosine 1-Phosphate Receptor Modulators
FDA EPC	N0000181816	Sphingosine 1-phosphate Receptor Modulator

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Secondary progressive multiple sclerosis	indication	425500002	DOID:0050783
Relapsing remitting multiple sclerosis	indication	426373005	DOID:2378
Sick sinus syndrome	contraindication	36083008	DOID:13884
Atrioventricular block	contraindication	233917008	DOID:0050820

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.28	acidic
pKa2	7.69	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 0.25MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	8492441	Nov. 30, 2030	A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE
EQ 1MG BASE	MAYZENT	NOVARTIS	N209884	Aug. 24, 2021	RX	TABLET	ORAL	8492441	Nov. 30, 2030	A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE
EQ 2MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	8492441	Nov. 30, 2030	A METHOD OF TREATING MULTIPLE SCLEROSIS BY ADMINISTERING SIPONIMOD USING A TITRATION SCHEME TO REACH A MAINTENANCE DOSE

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 0.25MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	March 26, 2024	NEW CHEMICAL ENTITY
EQ 1MG BASE	MAYZENT	NOVARTIS	N209884	Aug. 24, 2021	RX	TABLET	ORAL	March 26, 2024	NEW CHEMICAL ENTITY
EQ 2MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	March 26, 2024	NEW CHEMICAL ENTITY
EQ 0.25MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	March 1, 2025	REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130
EQ 1MG BASE	MAYZENT	NOVARTIS	N209884	Aug. 24, 2021	RX	TABLET	ORAL	March 1, 2025	REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130
EQ 2MG BASE	MAYZENT	NOVARTIS	N209884	March 26, 2019	RX	TABLET	ORAL	March 1, 2025	REVISIONS TO THE LABELING TO INCLUDE RESULTS FROM CLINICAL STUDY CBAF312A2130

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Sphingosine 1-phosphate receptor 1	GPCR	P21453	S1PR1_HUMAN	MODULATOR	EC50	9.41	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 5	GPCR	Q9H228	S1PR5_HUMAN	MODULATOR	EC50	9.01	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 4	GPCR	O95977	S1PR4_HUMAN	MODULATOR	EC50	6.13	SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 3	GPCR	Q99500	S1PR3_HUMAN	MODULATOR	EC50	3	SCIENTIFIC LITERATURE
Sphingosine 1-phosphate receptor 2	GPCR	O95136	S1PR2_HUMAN	MODULATOR	EC50	4	SCIENTIFIC LITERATURE

External reference:

ID	Source
RR6P8L282I	UNII
1234627-85-0	SECONDARY_CAS_RN
C3657824	UMLSCUI
J8C	PDB_CHEM_ID
CHEMBL2336071	ChEMBL_ID
44599207	PUBCHEM_CID
DB12371	DRUGBANK_ID
CHEMBL4298150	ChEMBL_ID
D11072	KEGG_DRUG
9491	INN_ID
9289	IUPHAR_LIGAND_ID
017942	NDDF
017943	NDDF
786997005	SNOMEDCT_US
787019001	SNOMEDCT_US
4038283	VANDF
2121085	RXNORM
312581	MMSL
36617	MMSL
d09219	MMSL
C578989	MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0979	TABLET, FILM COATED	0.25 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0979	TABLET, FILM COATED	0.25 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0979	TABLET, FILM COATED	0.25 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0979	TABLET, FILM COATED	0.25 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0986	TABLET, FILM COATED	2 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0986	TABLET, FILM COATED	2 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0986	TABLET, FILM COATED	2 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0986	TABLET, FILM COATED	2 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-1014	TABLET, FILM COATED	1 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-1014	TABLET, FILM COATED	1 mg	ORAL	NDA	30 sections
MAYZENT	HUMAN PRESCRIPTION DRUG LABEL	1	0078-1014	TABLET, FILM COATED	1 mg	ORAL	NDA	30 sections