daratumumab Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
human origin	5063	945721-28-8

Description:

Molecule	Description
Synonyms: daratumumab HuMax-CD38 3003-005 darzalex	Daratumumab is an IgG1k human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP). Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Synonyms:

daratumumab
HuMax-CD38
3003-005
darzalex

Daratumumab is an IgG1k human monoclonal antibody (mAb) that binds to CD38 and inhibits the growth of CD38 expressing tumor cells by inducing apoptosis directly through Fc mediated cross linking as well as by immune-mediated tumor cell lysis through complement dependent cytotoxicity (CDC), antibody dependent cell mediated cytotoxicity (ADCC) and antibody dependent cellular phagocytosis (ADCP).

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company
Sept. 27, 2017	PMDA	Janssen Pharmaceutical KK
May 20, 2016	EMA	Janssen-Cilag International N.V.
Nov. 16, 2015	FDA	JANSSEN BIOTECH

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
Plasma cell myeloma	814.63	20.10	333	11338	44145	46630246
Infusion related reaction	738.44	20.10	401	11270	100807	46573584
Neutropenia	244.70	20.10	235	11436	142969	46531422
Neuropathy peripheral	181.75	20.10	163	11508	90730	46583661
White blood cell count decreased	159.78	20.10	167	11504	112064	46562327
Neutrophil count decreased	149.08	20.10	107	11564	43319	46631072
Pneumonia	139.14	20.10	296	11375	376024	46298367
Platelet count decreased	139.04	20.10	147	11524	99877	46574514
Thrombocytopenia	128.40	20.10	158	11513	126423	46547968
Crossmatch incompatible	124.95	20.10	19	11652	20	46674371
Plasma cell myeloma recurrent	103.82	20.10	34	11637	2373	46672018
Coombs indirect test positive	95.10	20.10	15	11656	24	46674367
Tumour lysis syndrome	85.72	20.10	40	11631	7196	46667195
Off label use	75.60	20.10	237	11434	379604	46294787
Plasma cell leukaemia	72.94	20.10	22	11649	1171	46673220
Disease progression	72.31	20.10	101	11570	91199	46583192
Body dysmorphic disorder	67.30	20.10	14	11657	155	46674236
Febrile neutropenia	63.76	20.10	97	11574	94530	46579861
Cytopenia	62.47	20.10	33	11638	7735	46666656
Plasmacytoma	60.78	20.10	23	11648	2454	46671937
COVID-19	59.65	20.10	44	11627	18531	46655860
Morganella infection	53.05	20.10	14	11657	456	46673935
Product use in unapproved indication	49.13	20.10	84	11587	90189	46584202
Endocarditis bacterial	45.27	20.10	13	11658	582	46673809
Bronchospasm	43.36	20.10	34	11637	15673	46658718
Full blood count decreased	42.62	20.10	39	11632	22172	46652219
Joint ankylosis	41.47	20.10	12	11659	552	46673839
Cytomegalovirus infection	41.09	20.10	35	11636	18109	46656282
Pseudomyopia	41.02	20.10	8	11663	62	46674329
Pyrexia	38.03	20.10	180	11491	348622	46325769
Acute myopia	37.86	20.10	8	11663	96	46674295
Toxicity to various agents	36.24	20.10	5	11666	211761	46462630
Sepsis	35.74	20.10	94	11577	135920	46538471
Anaemia	34.70	20.10	141	11530	255638	46418753
Light chain analysis increased	33.83	20.10	12	11659	1066	46673325
Intraductal proliferative breast lesion	32.62	20.10	15	11656	2607	46671784
Plasma cells decreased	32.25	20.10	6	11665	35	46674356
Drug hypersensitivity	31.23	20.10	11	11660	243814	46430577
Visceral leishmaniasis	30.44	20.10	9	11662	447	46673944
Coombs direct test positive	30.07	20.10	6	11665	53	46674338
Meningitis cryptococcal	28.97	20.10	11	11660	1184	46673207
Laboratory test abnormal	28.89	20.10	32	11639	22815	46651576
Diarrhoea	28.24	20.10	237	11434	559365	46115026
Septic shock	26.52	20.10	50	11621	57843	46616548
Adverse drug reaction	26.41	20.10	43	11628	44319	46630072
Polyneuropathy	25.42	20.10	22	11649	11622	46662769
Respiratory tract infection	24.95	20.10	34	11637	29938	46644453
Atrial fibrillation	24.60	20.10	69	11602	103521	46570870
Headache	24.48	20.10	52	11619	478300	46196091
Constipation	24.39	20.10	97	11574	174000	46500391
Light chain analysis	24.17	20.10	4	11667	10	46674381
COVID-19 pneumonia	23.77	20.10	13	11658	3262	46671129
Condition aggravated	22.55	20.10	17	11654	245035	46429356
Pancytopenia	22.54	20.10	59	11612	84999	46589392
Hypogammaglobulinaemia	22.38	20.10	15	11656	5423	46668968
Bone marrow failure	22.23	20.10	32	11639	29637	46644754
Death	21.84	20.10	151	11520	335397	46338994
Dyspnoea	21.69	20.10	210	11461	515338	46159053
Cardiac amyloidosis	21.12	20.10	7	11664	507	46673884
Drug ineffective	20.91	20.10	93	11578	677745	45996646
Hypoperfusion	20.60	20.10	9	11662	1388	46673003
Disseminated cryptococcosis	20.51	20.10	6	11665	287	46674104
Cytomegalovirus infection reactivation	20.14	20.10	9	11662	1463	46672928

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
Infusion related reaction	1107.76	17.94	486	13800	40078	29898114
Plasma cell myeloma	765.13	17.94	412	13874	53050	29885142
Pneumonia	131.28	17.94	402	13884	333904	29604288
White blood cell count decreased	128.27	17.94	178	14108	83769	29854423
Platelet count decreased	122.07	17.94	197	14089	105932	29832260
Neuropathy peripheral	117.59	17.94	156	14130	70319	29867873
Plasma cell myeloma recurrent	112.74	17.94	47	14239	3367	29934825
Neutropenia	110.64	17.94	210	14076	128330	29809862
Plasmacytoma	110.15	17.94	46	14240	3310	29934882
Neutrophil count decreased	88.32	17.94	105	14181	42349	29895843
Off label use	79.64	17.94	280	14006	249010	29689182
Disease progression	67.96	17.94	130	14156	79744	29858448
Light chain analysis increased	62.36	17.94	22	14264	998	29937194
Crossmatch incompatible	59.84	17.94	9	14277	0	29938192
Thrombocytopenia	58.24	17.94	170	14116	136874	29801318
Coombs indirect test positive	54.67	17.94	9	14277	7	29938185
Influenza	53.10	17.94	83	14203	43315	29894877
Chills	49.93	17.94	108	14178	72230	29865962
Sepsis	49.67	17.94	168	14118	146227	29791965
Monoclonal immunoglobulin present	45.83	17.94	17	14269	891	29937301
Tumour lysis syndrome	44.91	17.94	42	14244	12843	29925349
Respiratory tract infection	43.71	17.94	45	14241	15461	29922731
COVID-19	43.52	17.94	48	14238	17830	29920362
Cytomegalovirus infection	43.44	17.94	55	14231	23619	29914573
Pyrexia	41.69	17.94	261	14025	294228	29643964
Cytopenia	39.01	17.94	32	14254	8224	29929968
Plasma cell leukaemia	38.34	17.94	15	14271	910	29937282
Hypercalcaemia	32.95	17.94	35	14251	12460	29925732
Product use in unapproved indication	32.76	17.94	93	14193	73600	29864592
Polyneuropathy	32.75	17.94	34	14252	11789	29926403
Progressive multifocal leukoencephalopathy	32.61	17.94	30	14256	8983	29929209
Toxicity to various agents	31.71	17.94	23	14263	177160	29761032
Cerebral toxoplasmosis	31.64	17.94	15	14271	1457	29936735
Respirovirus test positive	31.53	17.94	7	14279	53	29938139
Febrile neutropenia	31.45	17.94	117	14169	106576	29831616
Full blood count decreased	31.21	17.94	38	14248	15679	29922513
Bronchospasm	30.95	17.94	31	14255	10307	29927885
Cytomegalovirus viraemia	30.90	17.94	24	14262	5705	29932487
Product use issue	29.79	17.94	67	14219	45949	29892243
Overdose	29.49	17.94	3	14283	84334	29853858
Product dose omission issue	28.27	17.94	102	14184	91529	29846663
Plasma cell myeloma refractory	27.31	17.94	6	14280	43	29938149
Diverticular perforation	25.62	17.94	17	14269	3160	29935032
Infusion site thrombosis	25.21	17.94	5	14281	20	29938172
Oropharyngeal discomfort	25.20	17.94	13	14273	1514	29936678
Blood immunoglobulin G decreased	24.65	17.94	11	14275	929	29937263
Laboratory test abnormal	23.63	17.94	35	14251	17407	29920785
Infection	23.31	17.94	86	14200	77988	29860204
Pancytopenia	23.18	17.94	91	14195	84961	29853231
Blood immunoglobulin M increased	23.03	17.94	7	14279	197	29937995
Oxygen saturation decreased	22.47	17.94	58	14228	43382	29894810
Septic shock	22.39	17.94	74	14212	63533	29874659
Infusion site extravasation	21.62	17.94	14	14272	2499	29935693
Chloroma	21.23	17.94	8	14278	438	29937754
Lower respiratory tract infection	20.87	17.94	42	14244	26672	29911520
JC virus infection	20.57	17.94	12	14274	1778	29936414
Squamous cell carcinoma of skin	19.72	17.94	23	14263	9072	29929120
Sternal fracture	19.34	17.94	8	14278	561	29937631
Spinal compression fracture	19.22	17.94	19	14267	6215	29931977
Throat irritation	19.17	17.94	22	14264	8526	29929666
Therapy partial responder	18.90	17.94	15	14271	3676	29934516
Adverse drug reaction	18.81	17.94	37	14249	23108	29915084
Atrial fibrillation	18.55	17.94	101	14185	108023	29830169
Product preparation error	18.46	17.94	11	14275	1695	29936497
Cytomegalovirus chorioretinitis	18.30	17.94	14	14272	3254	29934938

Pharmacologic Action:

Source	Code	Description
ATC	L01XC24	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Monoclonal antibodies
FDA CS	M0001357	Antibodies, Monoclonal
MeSH PA	D000970	Antineoplastic Agents
FDA MoA	N0000192335	CD38-directed Antibody Interactions
FDA EPC	N0000192336	CD38-directed Cytolytic Antibody

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Multiple myeloma	indication	109989006	DOID:9538

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Lymphocyte differentiation antigen CD38	Tumour-associated antigen	P28907	CD38_HUMAN	ANTIBODY BINDING	Kd	8.22		IUPHAR	DRUG LABEL

External reference:

ID	Source
D10777	KEGG_DRUG
4035125	VANDF
C2346801	UMLSCUI
CHEMBL1743007	ChEMBL_ID
DB09331	DRUGBANK_ID
C556306	MESH_SUPPLEMENTAL_RECORD_UI
7395	IUPHAR_LIGAND_ID
9128	INN_ID
4Z63YK6E0E	UNII
1721947	RXNORM
237137	MMSL
31294	MMSL
d08399	MMSL
016591	NDDF
716016006	SNOMEDCT_US
781328004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
DARZALEX	HUMAN PRESCRIPTION DRUG LABEL	1	57894-502	INJECTION, SOLUTION, CONCENTRATE	100 mg	INTRAVENOUS	BLA	32 sections
Darzalex Faspro	HUMAN PRESCRIPTION DRUG LABEL	2	57894-503	INJECTION	1800 mg	SUBCUTANEOUS	BLA	32 sections