Daratumumab

Identification

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

Daratumumab is an anti-cancer drug indicated for multiple myeloma in patients who have received at least 3 prior treatments. It was granted accelerated approval by the FDA in November 2016. Marketed under the brand name Darzalex by Janssen Biotech, daratumumab is the first monoclonal antibody injection approved for this indication and provides another options for patients with multiple myeloma resistant to other therapies. Daratumumab induces apoptosis of cancer cells by targeting the CD38 epitope, which is highly expressed on haematological malignancies.

Protein structure
Db09331
Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
>Daratumumab heavy chain
EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ
YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Daratumumab light chain
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA
RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
HuMax-CD 38 / HuMax-CD38 / JNJ-54767414
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
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
DarzalexInjection, solution, concentrate100 mg/5mLIntravenousJanssen Biotech, Inc.2015-11-16Not applicableUs
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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Categories
UNII
4Z63YK6E0E
CAS number
945721-28-8

Pharmacology

Indication

For the treatment of patients with multiple myeloma who have received at least three prior lines of therapy (a proteasome inhibitor (PI) and an immunomodulatory agent) or who are double-refractory to a PI and an immunomodulatory agent. This indication was approved by accelerated approval based on response rate.

Associated Conditions
Pharmacodynamics

In preclinical trials, daratumumab showed synergistic activity with other multiple myeloma therapies, notably lenalidomide. Daratumumab also causes lysis in other cells that express CD38: myeloid-derived suppressor cells, a subset of regulatory T-cells, and NK cells. Decreases in absolute count and percentage of NK cells were observed during treatment. CD4+ and CD8+ T cell absolute counts as well the percentage of total lymphocytes increased in peripheral blood and bone marrow during daratumumab treatment.

Mechanism of action

Daratumumab is an immunoglobulin G1 kappa monoclonal antibody against CD38 antigen. CD38 is a transmembrane glycoprotein of many functions, including receptor mediated adhesion, signaling, and modulation of cyclase and hydrolase activity. CD38 is expressed on many cell types and tissues, and highly expressed in haematological malignancies including multiple myeloma tumor cells. By binding CD38, daratumumab causes inhibition of tumor cell growth and induces broad-spectrum apoptosis in multiple ways: by Fc-mediated cross linking, by immune-mediate tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell cytotoxicity, and antibody dependent cellular phagocytosis.

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

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Absorption

Following the recommended schedule and dose of 16 mg/kg, the mean serum Cmax value was 915 μg/mL at the end of weekly dosing, approximately 2.9-fold higher than following the first infusion. The mean predose serum concentration at the end of weekly dosing was 573 μg/mL.

Volume of distribution

4.7 L

Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Approximately 18 days.

Clearance

171.4 mL/day. Clearance decreased with increasing dose and repeated dosing, indicating target-mediated pharmacokinetics.

Toxicity

Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Due to its mechanism of action, daratumumab may cause fetal myeloid or lymphoid-cell depletion and decreased bone density. The FDA label recommends to defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed. Women of reproductive potential should also should use effective contraception methods during treatment and 3 months post-treatment to avoid pregnancy and exposure to the fetus while on daratumumab.

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

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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

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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]
External Links
PubChem Substance
347910441
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
0Not Yet RecruitingTreatmentAnn 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 RecruitingTreatmentMultiple Myeloma (MM)5
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentMultiple Myeloma (MM)2
1Not Yet RecruitingTreatmentAllosensitization / Heart Transplant Failure and Rejection1
1Not Yet RecruitingTreatmentMultiple Myeloma (MM)2
1RecruitingDiagnosticPlasma Cell Myeloma / Recurrent Plasma Cell Myeloma / Secondary amyloidosis1
1RecruitingTreatmentAdenocarcinoma 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
1RecruitingTreatmentAmyloid Light Chain (AL) Amyloidosis / Hematopoietic/Lymphoid Cancer / Newly Diagnosed Primary Amyloidosis / Recurrent Primary Amyloidosis / Refractory Primary Amyloidosis1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
1RecruitingTreatmentLymphoma, B-Cell / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentMultiple Myeloma (MM)2
1RecruitingTreatmentMultiple Myeloma (MM) / Non Hodgkin Lymphoma (NHL)1
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 RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Active Not RecruitingTreatmentLymphoma, Hodgkins / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1, 2Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
1, 2RecruitingDiagnosticMultiple Myeloma (MM)1
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)4
1, 2RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
1, 2RecruitingTreatmentRelapsed Refractory Multiple Myeloma1
1, 2RecruitingTreatmentVarious Advanced Cancer1
1, 2SuspendedTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
2Active Not RecruitingTreatmentAmyloidosis1
2Active Not RecruitingTreatmentDeletion 17P Syndrome / Multiple Myeloma (MM)1
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 RecruitingTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)6
2Active Not RecruitingTreatmentMultiple Myeloma (MM) / Smoldering Multiple Myeloma (SMM)1
2Active Not RecruitingTreatmentMyelodysplastic Syndromes1
2Active Not RecruitingTreatmentPlasma Cell Myeloma1
2CompletedTreatmentMultiple Myeloma (MM)3
2CompletedTreatmentPlasma Cell Myeloma1
2Not Yet RecruitingTreatmentLight Chain (AL) Amyloidosis, Stage 3B1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)6
2Not Yet RecruitingTreatmentMultiple Myeloma (MM) / Plasma Cell Myeloma1
2Not Yet RecruitingTreatmentNeoplastic Plasma Cells 30 Percent or More of Bone Marrow Nucleated Cells / Recurrent Plasma Cell Myeloma1
2RecruitingPreventionMultiple Myeloma (MM)1
2RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Acute, recurrent Myeloid Leukemia / Hematopoietic/Lymphoid Cancer / High Risk Myelodysplastic Syndrome / High-risk Myelodysplastic Syndrome / Refractory Acute Myeloid Leukemia1
2RecruitingTreatmentAlzheimer's Disease (AD)1
2RecruitingTreatmentCancer - Multiple Myeloma / Multiple Myeloma (MM)1
2RecruitingTreatmentDaratumumab / Multiple Myeloma in Relapse / Plasmacytoma1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2RecruitingTreatmentMembranoproliferative Glomerulonephritis1
2RecruitingTreatmentMinimal Residual Disease / Plasma Cell Myeloma1
2RecruitingTreatmentMonoclonal Gammopathy / Smoldering Multiple Myeloma (SMM)1
2RecruitingTreatmentMultiple Myeloma (MM)16
2RecruitingTreatmentMultiple Myeloma (MM) / Plasma Cell Myeloma1
2RecruitingTreatmentMultiple Myeloma in Relapse1
2RecruitingTreatmentMyeloma Multiple1
2RecruitingTreatmentMyeloma Multiple / Myeloma, Plasma-Cell / Myeloma-Multiple / Plasma Cell Myeloma1
2RecruitingTreatmentNewly Diagnosed Multiple Myeloma1
2RecruitingTreatmentPlasma Cell Myeloma2
2RecruitingTreatmentPlasma Cell Myeloma / Secondary amyloidosis1
2RecruitingTreatmentPrecursor Cell Lymphoblastic Leukemia-Lymphoma1
2RecruitingTreatmentRecurrent Plasma Cell Myeloma1
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
2RecruitingTreatmentWaldenstrom'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
2RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
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)1
2, 3Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2, 3CompletedTreatmentMultiple Myeloma (MM)1
3Active Not RecruitingTreatmentAmyloidosis1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)8
3Active Not RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
3Active Not RecruitingTreatmentSmoldering Multiple Myeloma (SMM)1
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
3Not Yet RecruitingTreatmentMultiple Myeloma in Relapse1
3RecruitingTreatmentMultiple Myeloma (MM)5
3RecruitingTreatmentMultiple Myeloma Stage I1
3RecruitingTreatmentNewly Diagnosed Multiple Myeloma1
3RecruitingTreatmentSmoldering Plasma Cell Myeloma1
3SuspendedTreatmentMultiple Myeloma (MM)1
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
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 November 12, 2019 22:51