Elranatamab

Identification

Summary

Elranatamab is a bispecific antibody used to treat adults with relapsed or refractory multiple myeloma.

Brand Names
Elrexfio
Generic Name
Elranatamab
DrugBank Accession Number
DB15395
Background

Elranatamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. It is a humanized immunoglobulin 2-alanine kappa antibody derived from two monoclonal antibodies (mAbs), an anti-BCMA mAb and an anti-CD3 mAb,1 each of which contributes one heavy chain and one light chain to drug structure. The resulting 4-chain bispecific antibody is covalently linked via five inter-chain disulfide bonds.4 On August 14, 2023, the FDA granted accelerated approval to elranatamab for the treatment of multiple myeloma.5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6440H9958N1738O2010S49
Protein Average Weight
148500.0 Da (approximate)
Sequences
>Elranatamab heavy chain 1
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDYYMTWVRQAPGKGLEWVAFIRNRARGYTS
DHNPSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARDRPSYYVLDYWGQGTTVTVS
SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCRVRCPRCPAPPVAGPSV
FLFPPKPKDTLMISRTPEVTCVVVAVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTF
RVVSVLTVVHQDWLNGKEYKCKVSNKGLPSSIEKTISKTKGQPREPQVYTLPPSREEMTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSRLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
>Elranatamab heavy chain 2
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWVSAIGGSGGSLPY
ADIVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARYWPMDIWGQGTLVTVSSASTKG
PSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL
SSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCEVECPECPAPPVAGPSVFLFPPK
PKDTLMISRTPEVTCVVVAVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVL
TVVHQDWLNGKEYKCKVSNKGLPSSIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT
CEVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCS
VMHEALHNHYTQKSLSLSPGK
>Elranatamab light chain 1
DIVMTQSPDSLAVSLGERATINCKSSQSLFNVRSRKNYLAWYQQKPGQPPKLLISWASTR
ESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCKQSYDLFTFGSGTKLEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Elranatamab light chain 2
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLMYDASIRATGIP
DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYQSWPLTFGQGTKVEIKRTVAAPSVFIFP
PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG DRUG: Elranatamab [Link]
Download FASTA Format
Synonyms
  • ANTI-CD3/ANTI-BCMA BISPECIFIC MONOCLONAL ANTIBODY PF-06863135
  • B-CELL MATURATION ANTIGEN (BCMA) CLUSTER OF DIFFERENTIATION 3 (CD3) BISPECIFIC MONOCLONAL ANTIBODY (MAB) ANTI-BCMA/ANTI-CD3 BISPECIFIC MAB
  • IMMUNOGLOBULIN G2 (224-ARGININE,265-ALANINE,330-SERINE,331-SERINE), ANTI-(HUMAN CD3 ANTIGEN .EPSILON.-CHAIN) (HUMAN-MUS MUSCULUS MONOCLONAL PF-06863059 .GAMMA.2-CHAIN), DISULFIDE WITH HUMAN-MUS MUSCULUS MONOCLONAL PF-06863059 .KAPPA.-CHAIN, (223->217')(2
  • IMMUNOGLOBULIN G2-KAPPA, ANTI-(HOMO SAPIENS T-CELL SURFACE GLYCOPROTEIN CD3 EPSILON CHAIN CD3E (T-CELL SURFACE ANTIGEN T3/LEU-4 EPSILON CHAIN)), HUMAN-MUS MUSCULUS MONOCLONAL DISULFIDE WITH IMMUNOGLOBULIN G2-KAPPA, ANTI-(HOMO SAPIENS-TUMOR NECROSIS FACTO
External IDs
  • PF-06863135
  • RN 613
  • RN-613
  • RN613

Pharmacology

Indication

Elranatamab is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.4

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s).4

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory multiple myeloma••••••••••••••••••• ••••• •••• ••••• ••••• •• •••••••
Treatment ofRelapsed multiple myeloma••••••••••••••••••• ••••• •••• ••••• ••••• •• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Elranatamab works to prevent multiple myeloma tumour growth. It causes a transient elevation of circulating cytokines IL-2, IL-6, IL-8, IL-10, TNF-α, and IFN-γ.4

Mechanism of action

BCMA is a B cell maturation antigen that binds several ligands to activate various survival signalling pathways, including NF-kappa B, STAT3, ERK1/2, and AKT/PI3K signalling pathways. It is often overexpressed in malignant plasma B cells, including multiple myeloma cells, making it a promising therapeutic target for T-cell engaging antibodies.3 Elranatamab is a bispecific B-cell maturation antigen (BCMA)-directed T-cell engaging antibody.1,2 It binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. Elranatamab activated T-cells, caused pro-inflammatory cytokine release, and resulted in multiple myeloma cell lysis.4

TargetActionsOrganism
UTumor necrosis factor receptor superfamily member 17
antibody
Humans
UT-cell surface glycoprotein CD3
antibody
Humans
Absorption

Elranatamab exhibits dose-proportional pharmacokinetics over the dose range of 6 to 76 mg, which is 0.079 to 1 times the approved recommended dosage. In subjects who received a weekly dosing of 76 mg over 24 weeks, the maximum concentration of 33.6 mcg/mL was achieved at the end of the weekly dosing regimen. The mean (coefficient of variation [CV]%) Cmax was 3.8 (94%) mcg/mL at the first full 76 mg dose. At 24 weeks and steady-state, the Cmax was 33.6 (48%) mcg/mL and 20.1 (55%) mcg/mL.4

Following subcutaneous administration, the mean bioavailability of elranatamab was 56.2%. The Tmax ranged from three to seven days.

Volume of distribution

The mean (CV%) steady-state volume of distribution of elranatamab was 7.76 L (33%).4

Protein binding

Not Available

Metabolism

Elranatamab is expected to be metabolized into small peptides by catabolic pathways.4

Route of elimination

Not Available

Half-life

The mean (CV%) half-life of elranatamab is 22 (64%) days at a dose of 76 mg.4

Clearance

The mean (CV%) clearance is 0.324 L/day (100%) following 24 weeks dosing.4

Adverse Effects
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Toxicity

There is no information available regarding the acute toxicity and overdose of elranatamab.

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.
Not Available
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ElrexfioSolution76 mg / 1.9 mLSubcutaneousPfizer Canada UlcNot applicableNot applicableCanada flag
ElrexfioInjection, solution44 mg/1.1mLSubcutaneousPfizer Laboratories Div Pfizer Inc2023-08-15Not applicableUS flag
ElrexfioSolution44 mg / 1.1 mLSubcutaneousPfizer Canada UlcNot applicableNot applicableCanada flag
ElrexfioInjection, solution44 mg/1.1mLSubcutaneousU.S. Pharmaceuticals2023-08-15Not applicableUS flag
ElrexfioInjection, solution76 mg/1.9mLSubcutaneousPfizer Laboratories Div Pfizer Inc2023-08-15Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
Not Available

Chemical Identifiers

UNII
L0HR9A577V
CAS number
2408850-14-4

References

General References
  1. Grosicki S, Bednarczyk M, Kociszewska K: Elranatamab: a new promising BispAb in multiple myeloma treatment. Expert Rev Anticancer Ther. 2023 Jul 20:1-8. doi: 10.1080/14737140.2023.2236303. [Article]
  2. Lesokhin AM, Tomasson MH, Arnulf B, Bahlis NJ, Miles Prince H, Niesvizky R, Rodriotaguez-Otero P, Martinez-Lopez J, Koehne G, Touzeau C, Jethava Y, Quach H, Depaus J, Yokoyama H, Gabayan AE, Stevens DA, Nooka AK, Manier S, Raje N, Iida S, Raab MS, Searle E, Leip E, Sullivan ST, Conte U, Elmeliegy M, Czibere A, Viqueira A, Mohty M: Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023 Aug 15. doi: 10.1038/s41591-023-02528-9. [Article]
  3. Wu L, Huang Y, Sienkiewicz J, Sun J, Guiang L, Li F, Yang L, Golubovskaya V: Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Cancers (Basel). 2022 May 20;14(10). pii: cancers14102518. doi: 10.3390/cancers14102518. [Article]
  4. FDA Approved Drug Products: ELREXFIO (elranatamab-bcmm) injection, for subcutaneous use [Link]
  5. FDA: FDA grants accelerated approval to elranatamab-bcmm for multiple myeloma [Link]
RxNav
2644880
Wikipedia
Elranatamab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentMultiple Myeloma (MM)1
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentMultiple Myeloma (MM)3
2Active Not RecruitingTreatmentBCMA / BCMA-CD3 Bispecific / Bispecific / Bispecific Antibody / Elranatamab / MagnetisMM-8 / Multiple Myeloma (MM) / PF-06863135 / Refractory Multiple Myeloma / Relapsed Multiple Myeloma1
2Active Not RecruitingTreatmentMultiple Myeloma (MM)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous44 mg/1.1mL
Injection, solutionSubcutaneous76 mg/1.9mL
SolutionSubcutaneous44 mg / 1.1 mL
SolutionSubcutaneous76 mg / 1.9 mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antibody
General Function
Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.
Specific Function
Signaling receptor activity
Gene Name
TNFRSF17
Uniprot ID
Q02223
Uniprot Name
Tumor necrosis factor receptor superfamily member 17
Molecular Weight
20165.065 Da
References
  1. FDA Approved Drug Products: ELREXFIO (elranatamab-bcmm) injection, for subcutaneous use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antibody
General Function
Transmembrane signaling receptor activity
Specific Function
The CD3 complex mediates signal transduction.

Components:
References
  1. FDA Approved Drug Products: ELREXFIO (elranatamab-bcmm) injection, for subcutaneous use [Link]

Drug created at May 20, 2019 15:24 / Updated at August 19, 2023 10:38