Identification

Name
Elotuzumab
Accession Number
DB06317
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Elotuzumab is a humanized IgG1 (Immunoglobulin G) monoclonal antibody indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies. Elotuzumab targets SLAMF7, also known as Signaling Lymphocytic Activation Molecule Family member 7, a cell surface glycoprotein. Elotuzumab consists of the complementary determining regions (CDR) of the mouse antibody, MuLuc63, grafted onto human IgG1 heavy and kappa light chain frameworks. Elotuzumab is produced in NS0 cells by recombinant DNA technology. Elotuzumab has a theoretical mass of 148.1 kDa for the intact antibody. Elotuzumab was approved on November 30, 2015 by the U.S. Food and Drug Administration. Elotuzumab is marketed under the brand Emplicitiā„¢ by Bristol-Myers Squibb.

Protein structure
Db06317
Protein chemical formula
C6476H9982N1714O2016S42
Protein average weight
148100.0 Da
Sequences
>Elotuzumab heavy chain
EVQLVESGGGLVQPGGSLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINY
APSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Elotuzumab light chain
DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPD
RFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • HuLuc63
  • Immunoglobulin G1, anti-(human protein CS1) (human-mouse HuLuc63 heavy chain), disulfide with human-mouse HuLuc63 kappa-chain, dimer
  • Immunoglobulin G1, anti-(human SLAM family member 7 (CD2-like receptor activating cytotoxic cells, CD319 antigen)), humanized mouse monoclonal HuLuc63 gamma-1 heavy chain (222-214')-disulfide with humanized mouse monoclonal HuLuc63 kappa light chain (228-228'';231-231'')-bisdisulfide dimer
External IDs
BMS-901608 / PDL 063 / PDL063 / UNII-1351PE5UGS
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EmplicitiPowder, for solution340 mgIntravenousBristol Myers SquibbNot applicableNot applicableCanada
EmplicitiInjection, powder, for solution300 mgIntravenousBristol Myers Squibb2016-05-11Not applicableEu
EmplicitiInjection, powder, lyophilized, for solution400 mg/1IntravenousE.R. Squibb & Sons, L.L.C.2015-11-30Not applicableUs
EmplicitiPowder, for solution440 mgIntravenousBristol Myers SquibbNot applicableNot applicableCanada
EmplicitiInjection, powder, lyophilized, for solution300 mg/1IntravenousE.R. Squibb & Sons, L.L.C.2015-11-30Not applicableUs
EmplicitiInjection, powder, for solution400 mgIntravenousBristol Myers Squibb2016-05-11Not applicableEu
Categories
UNII
1351PE5UGS
CAS number
915296-00-3

Pharmacology

Indication

Indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (Signaling Lymphocytic Activation Molecule Family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on Natural Killer cells, plasma cells, and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates Natural Killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with Natural Killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, the combination of elotuzumab and lenalidomide resulted in enhanced activation of Natural Killer cells that was greater than the effects of either agent alone and increased anti-tumor activity in vitro and in vivo.

TargetActionsOrganism
ASLAM family member 7
modulator
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance

The clearance of elotuzumab decreased from a geometric mean (CV%) of 17.5 (21.2%) to 5.8 (31%) mL/day/kg with an increase in dose from 0.5 (i.e., 0.05 times the recommended dosage) to 20 mg/kg (i.e., 2 times the recommended dosage). Based on a population PK model, when elotuzumab is given in combination with lenalidomide and dexamethasone, approximately 97% of the maximum steady-state concentration is predicted to be eliminated with a geometric mean (CV%) of 82.4 (48%) days.

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

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Elotuzumab.
AbituzumabThe risk or severity of adverse effects can be increased when Elotuzumab is combined with Abituzumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Elotuzumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Elotuzumab.
AducanumabThe risk or severity of adverse effects can be increased when Elotuzumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Elotuzumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Elotuzumab.
AlirocumabThe risk or severity of adverse effects can be increased when Elotuzumab is combined with Alirocumab.
AmatuximabThe risk or severity of adverse effects can be increased when Elotuzumab is combined with Amatuximab.
AMG 108The risk or severity of adverse effects can be increased when AMG 108 is combined with Elotuzumab.
Food Interactions
Not Available

References

Synthesis Reference

"Patent Link":https://www.google.com/patents/WO2014055370A1?cl=en

General References
  1. Hsi ED, Steinle R, Balasa B, Szmania S, Draksharapu A, Shum BP, Huseni M, Powers D, Nanisetti A, Zhang Y, Rice AG, van Abbema A, Wong M, Liu G, Zhan F, Dillon M, Chen S, Rhodes S, Fuh F, Tsurushita N, Kumar S, Vexler V, Shaughnessy JD Jr, Barlogie B, van Rhee F, Hussein M, Afar DE, Williams MB: CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008 May 1;14(9):2775-84. doi: 10.1158/1078-0432.CCR-07-4246. [PubMed:18451245]
  2. Tai YT, Dillon M, Song W, Leiba M, Li XF, Burger P, Lee AI, Podar K, Hideshima T, Rice AG, van Abbema A, Jesaitis L, Caras I, Law D, Weller E, Xie W, Richardson P, Munshi NC, Mathiot C, Avet-Loiseau H, Afar DE, Anderson KC: Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood. 2008 Aug 15;112(4):1329-37. Epub 2007 Sep 28. [PubMed:17906076]
  3. Markham A: Elotuzumab: First Global Approval. Drugs. 2016 Mar;76(3):397-403. doi: 10.1007/s40265-016-0540-0. [PubMed:26809244]
External Links
KEGG Drug
D09337
PubChem Substance
347910347
ChEMBL
CHEMBL1743010
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Elotuzumab
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (245 KB)
MSDS
Download (381 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMultiple Myeloma (MM)5
1TerminatedTreatmentMultiple Myeloma (MM)2
1, 2Active Not RecruitingTreatmentDS Stage I Plasma Cell Myeloma / DS Stage II Plasma Cell Myeloma / DS Stage III Plasma Cell Myeloma / Multiple Myeloma (MM) / Plasma Cell Myeloma1
1, 2RecruitingTreatmentPlasma Cell Myeloma1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)4
2Active Not RecruitingTreatmentRelapsed and/or Refractory Multiple Myeloma1
2Active Not RecruitingTreatmentSmoldering Multiple Myeloma (SMM) / Smoldering Myeloma1
2CompletedTreatmentHematologic Cancers1
2CompletedTreatmentMultiple Myeloma (MM)2
2CompletedTreatmentSmoldering Multiple Myeloma (SMM)1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)2
2Not Yet RecruitingTreatmentRefractory Plasma Cell Myeloma1
2RecruitingSupportive CareMultiple Myeloma (MM)1
2RecruitingTreatmentHematopoietic Cell Transplantation Recipient / Plasma Cell Myeloma1
2RecruitingTreatmentMultiple Myeloma (MM)7
2RecruitingTreatmentMultiple Myeloma in Relapse2
2RecruitingTreatmentRecurrent Primary Amyloidosis1
2WithdrawnTreatmentMultiple Myeloma (MM)2
3Active Not RecruitingBasic ScienceNewly Diagnosed, Previously Untreated Multiple Myeloma1
3Active Not RecruitingTreatmentLymphoma (Myeloma) / Malignant Lymphomas / Multiple Myeloma (MM)1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)3
Not AvailableAvailableNot AvailableMultiple Myeloma (MM)2
Not AvailableNo Longer AvailableNot AvailableMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous300 mg
Injection, powder, for solutionIntravenous400 mg
Injection, powder, lyophilized, for solutionIntravenous300 mg/1
Injection, powder, lyophilized, for solutionIntravenous400 mg/1
Powder, for solutionIntravenous340 mg
Powder, for solutionIntravenous440 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US2014055370No2012-10-012032-10-01Us

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
Human
Pharmacological action
Yes
Actions
Modulator
General Function
Not Available
Specific Function
Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differ...
Gene Name
SLAMF7
Uniprot ID
Q9NQ25
Uniprot Name
SLAM family member 7
Molecular Weight
37420.62 Da
References
  1. Markham A: Elotuzumab: First Global Approval. Drugs. 2016 Mar;76(3):397-403. doi: 10.1007/s40265-016-0540-0. [PubMed:26809244]

Drug created on March 19, 2008 10:24 / Updated on November 20, 2018 00:55