Identification
NameDaratumumab
Accession NumberDB09331
TypeBiotech
GroupsApproved
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 structureDb09331
Related Articles
Protein chemical formulaNot Available
Protein average weightNot Available
SequencesNot Available
Synonyms
HuMax-CD38
External IDs JNJ-54767414
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DarzalexInjection, solution, concentrate20 mg/mlIntravenousJanssen Cilag International Nv2016-05-20Not applicableEu
DarzalexSolution100 mgIntravenousJanssen Pharmaceuticals2016-07-12Not applicableCanada
DarzalexInjection, solution, concentrate20 mg/mlIntravenousJanssen Cilag International Nv2016-05-20Not applicableEu
DarzalexSolution400 mgIntravenousJanssen Pharmaceuticals2016-07-12Not applicableCanada
DarzalexInjection, solution, concentrate100 mg/5mLIntravenousJanssen Biotech, Inc.2015-11-16Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII4Z63YK6E0E
CAS number945721-28-8
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.

Structured Indications Not Available
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
ADP-ribosyl cyclase 1Proteinunknown
antibody
HumanP28907 details
Related Articles
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 bindingNot Available
MetabolismNot Available
Route of eliminationNot 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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Daratumumab.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Daratumumab.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Daratumumab.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Daratumumab.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Daratumumab.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Daratumumab.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Daratumumab.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Daratumumab.Approved, Investigational
G17DTThe therapeutic efficacy of G17DT can be decreased when used in combination with Daratumumab.Investigational
GI-5005The therapeutic efficacy of GI-5005 can be decreased when used in combination with Daratumumab.Investigational
INGN 201The therapeutic efficacy of INGN 201 can be decreased when used in combination with Daratumumab.Investigational
INGN 225The therapeutic efficacy of INGN 225 can be decreased when used in combination with Daratumumab.Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Daratumumab.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Daratumumab.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Daratumumab.Approved, Vet Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Daratumumab.Approved
RindopepimutThe therapeutic efficacy of CDX-110 can be decreased when used in combination with Daratumumab.Investigational
SRP 299The therapeutic efficacy of SRP 299 can be decreased when used in combination with Daratumumab.Investigational
TG4010The therapeutic efficacy of TG4010 can be decreased when used in combination with Daratumumab.Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Daratumumab.Approved, Investigational
Food InteractionsNo interactions found.
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS Codes
  • 10:00
PDB EntriesNot Available
FDA labelDownload (417 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentLymphoma, Hodgkins / Multiple Myeloma (MM) / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentMultiple Myeloma (MM)1
1Not Yet RecruitingTreatmentMonoclonal Gammopathy / Smoldering Multiple Myeloma (SMM)1
1RecruitingTreatmentAdenocarcinoma of the Prostate / Malignant Neoplasms of Male Genital Organs / Prostate Cancer1
1RecruitingTreatmentMultiple Myeloma (MM)7
1, 2RecruitingTreatmentAL Amyloidosis1
1, 2RecruitingTreatmentCancer, Advanced1
1, 2RecruitingTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
1, 2RecruitingTreatmentVarious Advanced Cancer1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
2Active Not RecruitingTreatmentMultiple Myeloma (MM) / Smoldering Multiple Myeloma (SMM)1
2Not Yet RecruitingTreatmentAcute Myelogenous Leukaemia (AML) / Hematopoietic/Lymphoid Cancer / High-risk Myelodysplastic Syndrome1
2Not Yet RecruitingTreatmentMalignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
2Not Yet RecruitingTreatmentMembranoproliferative Glomerulonephritis1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)4
2Not Yet RecruitingTreatmentPlasma Cell Myeloma1
2Not Yet RecruitingTreatmentWaldenstrom's Macroglobulinemia (WM)1
2RecruitingTreatmentAmyloidosis1
2RecruitingTreatmentMicrosatellite 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
2RecruitingTreatmentMalignant Lymphomas1
2RecruitingTreatmentMultiple Myeloma (MM)7
2RecruitingTreatmentMyelodysplastic Syndromes1
2RecruitingTreatmentPlasma Cell Myeloma1
2TerminatedTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Lymphoma, Mantle-Cell1
2WithdrawnTreatmentMalignant Neoplasms of Male Genital Organs / Prostate Cancer1
2, 3RecruitingTreatmentMultiple Myeloma (MM)1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)3
3Not Yet RecruitingTreatmentAmyloidosis1
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)3
3RecruitingTreatmentMultiple Myeloma (MM)3
3RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1
Not AvailableAvailableNot AvailableMultiple Myeloma (MM)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous100 mg/5mL
Injection, solution, concentrateIntravenous20 mg/ml
SolutionIntravenous100 mg
SolutionIntravenous400 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
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 activity. Also moonlights as a receptor in cells of the immune system.
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 August 17, 2016 12:24