Daratumumab

Identification

Name
Daratumumab
Accession Number
DB09331
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Daratumumab is an immunoglobulin G1 kappa monoclonal antibody developed by Janssen and Genmab.1 It was first described in the literature in 2010 as a monoclonal antibody that targets CD38+ multiple myeloma cells; the first of its kind.5

Daratumumab was granted FDA approval on 16 November 2015.6

Protein structure
Db09331
Protein chemical formula
C6466H9996N1724O2010S42
Protein average weight
145391.67 Da
Sequences
>Daratumumab heavy chain
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Daratumumab light chain
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Daratumumab
External IDs
HuMax-CD 38 / HuMax-CD38 / JNJ-54767414
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DarzalexInjection, solution, concentrate100 mg/5mLIntravenousJanssen Biotech, Inc.2015-11-16Not applicableUs
DarzalexInjection, solution, concentrate20 mg/mlIntravenousJanssen Cilag International Nv2016-05-20Not applicableEu
DarzalexInjection, solution, concentrate20 mg/mlIntravenousJanssen Cilag International Nv2016-05-20Not applicableEu
DarzalexSolution400 mgIntravenousJanssen Pharmaceuticals2016-07-12Not applicableCanada
DarzalexSolution100 mgIntravenousJanssen Pharmaceuticals2016-07-12Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Darzalex FasproDaratumumab (1800 mg/15mL) + Hyaluronidase (human recombinant) (30000 U/15mL)InjectionSubcutaneousJanssen Biotech, Inc.2020-05-01Not applicableUs
Categories
UNII
4Z63YK6E0E
CAS number
945721-28-8

Pharmacology

Indication

Daratumumab is indicated as an intravenous injection alone or in combination with other medications for the treatment of multiple myeloma.6 Subcutaneous daratumumab with hyaluronidase is also indicated alone or in combination for the treatment of multiple myeloma.7

Associated Conditions
Pharmacodynamics

Daratumumab is a monoclonal antibody that targets and induces apoptosis in cells that highly express CD38, including multiple myeloma cells.6,7 It has a long duration of action as it is given every 1-4 weeks.6,7 Patients should be counselled regarding the risk of hypersensitivity, neutropenia, thrombocytopenia, embryo-fetal toxicity, and interferences with cross-matching and red blood cell antibody screening.6,7

Mechanism of action

CD38 is a glycoprotein present on the surface of hematopoietic cells and is responsible for a number of cell signalling functions.1,2,3,6,7 Daratumumab is an immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets CD38.3 Cancers like multiple myeloma overexpress CD38, allowing daratumumab to have higher affinity for these cells.3 This binding allows daratumumab to induce apoptosis, antibody dependent cellular phagocytosis, and antibody and complement-dependent cytotoxicity.2,3,6,7 Antibody dependent cellular phagocytosis is mediated by the FC region of the antibody inducing phagocytes such as macrophages, antibody dependent cellular cytotoxicity is mediated by the FC region of the antibody inducing effector cells such as natural killer cells, and complement dependent cytotoxicity is mediated by the FC region of the antibody binding to and inducing complement protein activity.1,2,3

TargetActionsOrganism
UADP-ribosyl cyclase 1
antibody
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Subcutaneous daratumumab reaches a Cmax of 592µg/mL compared to intravenous daratumumab, which reaches a Cmax of 688µg/mL.7 The AUC of subcutaneous daratumumab is 4017µg/mL*day compared to intravenous daratumumab, which has an AUC of 4019µg/mL*day.7

Volume of distribution

Daratumumab intravenous monotherapy has a volume of distribution of 4.7 ± 1.3L and the combination therapy has a volume of distribution of 4.4 ± 1.5L.6 Subcutaneous daratumumab has a volume of distribution of the central compartment of 5.2L and a volume of distribution of the peripheral compartment of 3.8L.7

Protein binding

Data regarding protein binding of daratumumab in serum is not readily available.6,7

Metabolism

Monoclonal antibodies are expected to be metabolized to smaller proteins and amino acids by proteolytic enzymes.4

Route of elimination

Monoclonal antibodies are metabolized to amino acids used for synthesis of new proteins or are eliminated by the kidneys.4

Half life

Intravenous daratumumab has a terminal half life of 18 ± 9 days.6 Subcutaneous daratumumab has a half life of 20 days.7

Clearance

Intravenous daratumumab has a clearance of 171.4 ± 95.3mL/day.6 Subcutaneous daratumumab has a clearance of 119mL/day.7

Toxicity

Data regarding overdoses of daratumumab are not readily available.6,7 Patients should be treated with symptomatic and supportive measures.6,7

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Daratumumab.
AbituzumabThe risk or severity of adverse effects can be increased when Daratumumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Daratumumab is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Daratumumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Daratumumab.
AducanumabThe risk or severity of adverse effects can be increased when Daratumumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Daratumumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Daratumumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Daratumumab.
AmatuximabThe risk or severity of adverse effects can be increased when Daratumumab is combined with Amatuximab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
No interactions found.

References

General References
  1. McKeage K: Daratumumab: First Global Approval. Drugs. 2016 Feb;76(2):275-81. doi: 10.1007/s40265-015-0536-1. [PubMed:26729183]
  2. Phipps C, Chen Y, Gopalakrishnan S, Tan D: Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. Ther Adv Hematol. 2015 Jun;6(3):120-7. doi: 10.1177/2040620715572295. [PubMed:26137203]
  3. de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, Oomen LA, Peipp M, Valerius T, Slootstra JW, Mutis T, Bleeker WK, Anderson KC, Lokhorst HM, van de Winkel JG, Parren PW: Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011 Feb 1;186(3):1840-8. doi: 10.4049/jimmunol.1003032. Epub 2010 Dec 27. [PubMed:21187443]
  4. Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000. [PubMed:20608753]
  5. van der Veer MS, de Weers M, van Kessel B, Bakker JM, Wittebol S, Parren PW, Lokhorst HM, Mutis T: Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica. 2011 Feb;96(2):284-90. doi: 10.3324/haematol.2010.030759. Epub 2010 Nov 25. [PubMed:21109694]
  6. FDA Approved Drug Products: Darzalex Daratumumab Intravenous Injection [Link]
  7. FDA Approved Drug Products: Darzalex Faspro Daratumumab and Hyaluronidase-fihj Subcutaneous Injection [Link]
External Links
PubChem Substance
347910441
RxNav
1721947
ChEMBL
CHEMBL1743007
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Daratumumab
ATC Codes
L01XC24 — Daratumumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (417 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentAnn Arbor Stage I Diffuse Large B-Cell Lymphoma / Ann Arbor Stage II Diffuse Large B-Cell Lymphoma / Ann Arbor Stage III Diffuse Large B-Cell Lymphoma / Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma / Plasmablastic Lymphoma1
0RecruitingTreatmentBladder Urothelial Carcinoma / Clear Cell Renal Cell Carcinoma / Malignant Neoplasms of Urinary Tract / Malignant Urinary System Neoplasm / Metastatic Kidney Carcinoma / Stage IV Renal Cell Cancer AJCC v81
1Active Not RecruitingTreatmentAdenocarcinoma of the Prostate / Adenocarcinoma, Prostate / Malignant Neoplasms of Male Genital Organs / Prostate Cancer / Stage III Prostate Cancer AJCC v8 / Stage IIIA Prostate Cancer AJCC v8 / Stage IIIB Prostate Cancer AJCC v8 / Stage IIIC Prostate Cancer AJCC v8 / Testosterone Greater Than 150 ng/dL1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentMultiple Myeloma (MM)5
1Not Yet RecruitingTreatmentAllosensitization / Heart Transplant Failure and Rejection1
1RecruitingDiagnosticPlasma Cell Myeloma / Recurrent Plasma Cell Myeloma / Secondary amyloidosis1
1RecruitingTreatmentAmyloid Light Chain (AL) Amyloidosis / Hematopoietic/Lymphoid Cancer / Newly Diagnosed Primary Amyloidosis / Recurrent Primary Amyloidosis / Refractory Primary Amyloidosis1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
1RecruitingTreatmentIndolent Non-Hodgkin's Lymphomas / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentLymphoma, B-Cell / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMultiple Myeloma (MM)5
1SuspendedTreatmentBreast Adenocarcinoma / Recurrent Breast Carcinoma / Recurrent Hodgkin Lymphoma / Recurrent Mycosis Fungoides / Recurrent Non-Hodgkin Lymphoma / Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Refractory Hodgkin Lymphoma / Refractory Nodal Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory, advanced Mycosis fungoides / Refractory, primary Cutaneous T-Cell Non-Hodgkin Lymphoma / Stage IV Breast Cancer AJCC v6 and v71
1WithdrawnTreatmentLeukemia, Plasma Cell1
1, 2Active Not RecruitingTreatmentAL Amyloidosis1
1, 2Active Not RecruitingTreatmentCancer, Advanced1
1, 2Active Not RecruitingTreatmentLymphoma, Hodgkins / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1, 2Active Not RecruitingTreatmentVarious Advanced Cancer1
1, 2CompletedDiagnosticMultiple Myeloma (MM)1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2RecruitingTreatmentAllosensitization / Antibody-mediated Rejection / Kidney Transplant Rejection1
1, 2RecruitingTreatmentMinimal Residual Disease / Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Myeloid Leukemia1
1, 2RecruitingTreatmentMultiple Myeloma (MM)5
1, 2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma2
1, 2WithdrawnTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2Active Not RecruitingTreatmentAmyloidosis1
2Active Not RecruitingTreatmentDeletion 17P Syndrome / Multiple Myeloma (MM)1
2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2Active Not RecruitingTreatmentMicrosatellite Stable Colorectal Cancer / Microsatellite Unstable Colorectal Cancer / Mismatch Repair Deficient Colorectal Cancer / Mismatch Repair Proficient Colorectal Cancer / MSI Negative Colorectal Cancer / MSI Positive Colorectal Cancer1
2Active Not RecruitingTreatmentMembranoproliferative Glomerulonephritis1
2Active Not RecruitingTreatmentMonoclonal Gammopathy / Smoldering Multiple Myeloma (SMM)1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)9
2Active Not RecruitingTreatmentMultiple Myeloma (MM) / Myeloma, Plasma-Cell / Plasma Cell Myeloma1
2Active Not RecruitingTreatmentMultiple Myeloma in Relapse1
2Active Not RecruitingTreatmentMyelodysplastic Syndromes1
2Active Not RecruitingTreatmentPlasma Cell Myeloma2
2Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMultiple Myeloma (MM)3
2CompletedTreatmentPlasma Cell Myeloma1
2Not Yet RecruitingTreatmentAL Amyloidosis / Amyloid / Refractory AL Amyloidosis1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)6
2Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Multiple Myeloma in Relapse / Refractory Multiple Myeloma / Relapses1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Refractory Multiple Myeloma / Relapse Multiple Myeloma1
2Not Yet RecruitingTreatmentPOEMS Syndrome1
2Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma1
2Not Yet RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2Not Yet RecruitingTreatmentRecurrent Cutaneous T-cell lymphoma / Refractory T-Cell Lymphoma1
2RecruitingPreventionMultiple Myeloma (MM)1
2RecruitingTreatmentAlzheimer's Disease (AD)1
2RecruitingTreatmentDaratumumab / Multiple Myeloma in Relapse / Plasmacytoma1
2RecruitingTreatmentExtramedullary Plasmacytoma / Multiple Myeloma (MM)1
2RecruitingTreatmentAcute, recurrent Myeloid Leukemia / Hematopoietic/Lymphoid Cancer / High Risk Myelodysplastic Syndrome / High-risk Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Refractory Acute Myelogenous Leukemia (AML)1
2RecruitingTreatmentLight Chain (AL) Amyloidosis, Stage 3B1
2RecruitingTreatmentMinimal Residual Disease / Plasma Cell Myeloma1
2RecruitingTreatmentMultiple Myeloma (MM)18
2RecruitingTreatmentMultiple Myeloma (MM) / Plasma Cell Myeloma2
2RecruitingTreatmentNewly Diagnosed Multiple Myeloma1
2RecruitingTreatmentPlasma Cell Myeloma1
2RecruitingTreatmentPlasma Cell Myeloma / Renal Failure1
2RecruitingTreatmentPlasma Cell Myeloma / Secondary amyloidosis1
2RecruitingTreatmentPrecursor Cell Lymphoblastic Leukemia-Lymphoma1
2RecruitingTreatmentRecurrent Plasma Cell Myeloma2
2RecruitingTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2RecruitingTreatmentRefractory Multiple Myeloma1
2RecruitingTreatmentRelapse and / or Refractory Myeloma1
2RecruitingTreatmentRelapsed or Refractory Chronic Lymphocytic Leukemia (CLL)1
2RecruitingTreatmentRelapsed/Refractory Multiple Myeloma1
2RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
2SuspendedTreatmentWaldenstrom's Disease / Waldenstrom's Macroglobulinaemia, Without Mention of Remission / Waldenstrom's Macroglobulinemia of Lymph Nodes / Waldenstrom's Macroglobulinemia Recurrent / Waldenstrom's Macroglobulinemia Refractory / Waldenström's Macroglobulinemia (WM) / Waldenström; Hypergammaglobulinemia1
2TerminatedTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL)1
2WithdrawnTreatmentMalignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
2WithdrawnTreatmentMalignant Neoplasms of Male Genital Organs / Prostate Cancer1
2WithdrawnTreatmentMultiple Myeloma (MM)2
2, 3Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2, 3CompletedTreatmentMultiple Myeloma (MM)1
3Active Not RecruitingTreatmentAmyloidosis1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)11
3Active Not RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
3Active Not RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentMultiple Myeloma (MM)6
3RecruitingTreatmentMultiple Myeloma Stage I1
3RecruitingTreatmentMultiple Myeloma in Relapse1
3RecruitingTreatmentNewly Diagnosed Multiple Myeloma1
3RecruitingTreatmentSmoldering Plasma Cell Myeloma1
4RecruitingTreatmentMultiple Myeloma (MM)1
Not AvailableApproved for MarketingNot AvailableMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous100 mg/5mL
Injection, solution, concentrateIntravenous20 mg/ml
SolutionIntravenous100 mg
SolutionIntravenous400 mg
InjectionSubcutaneous
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antibody
General Function
Transferase activity
Specific Function
Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activ...
Gene Name
CD38
Uniprot ID
P28907
Uniprot Name
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Molecular Weight
34328.145 Da
References
  1. de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, Oomen LA, Peipp M, Valerius T, Slootstra JW, Mutis T, Bleeker WK, Anderson KC, Lokhorst HM, van de Winkel JG, Parren PW: Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011 Feb 1;186(3):1840-8. doi: 10.4049/jimmunol.1003032. Epub 2010 Dec 27. [PubMed:21187443]

Drug created on November 18, 2015 10:34 / Updated on July 03, 2020 22:11

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