Ramucirumab

Identification

Summary

Ramucirumab is an antineoplastic agent and direct VEGFR2 (vascular endothelial growth factor receptor 2) antagonist that blocks the binding of natural VEGF ligands, which are secreted by solid tumors to promote angiogenesis and enhance tumor blood supply.

Brand Names
Cyramza
Generic Name
Ramucirumab
DrugBank Accession Number
DB05578
Background

Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells. VEGFR stimulation also mediates downstream signalling required for angiogenesis and is postulated to be heavily involved in cancer progression, making it a highly likely drug target. In contrast to other agents directed against VEGFR-2, ramucirumab binds a specific epitope on the extracellular domain of VEGFR-2, thereby blocking all VEGF ligands from binding to it. Ramucirumab is indicated for us in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db05578
Protein Chemical Formula
C6374H9864N1692O1996S46
Protein Average Weight
143600.0 Da
Sequences
>9098_H|ramucirumab|Homo sapiens||H-GAMMA-1 (VH(1-116)+CH1(117-214)+HINGE-REGION(215-229)+CH2(230-339)+CH3(340-446))|||||||446||||MW 48696.0|MW 48696.0|
EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSSISSSSSYIYY
ADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARVTDAFDIWGQGTMVTVSSASTK
GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS
LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN
VFSCSVMHEALHNHYTQKSLSLSPGK
>9098_L|ramucirumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(109-214))|||||||214||||MW 23124.7|MW 23124.7|
DIQMTQSPSSVSASIGDRVTITCRASQGIDNWLGWYQQKPGKAPKLLIYDASNLDTGVPS
RFSGSGSGTYFTLTISSLQAEDFAVYFCQQAKAFPPTFGGGTKVDIKGTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Ramucirumab
External IDs
  • 1121B
  • IMC-1121B
  • LY3009806

Pharmacology

Indication

For use in advanced gastric or gastro-esophageal junction adenocarcinoma as a single agent or in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

Ramucirumab is a human monoclonal antibody (IgG1) against vascular endothelial growth factor receptor 2 (VEGFR2), a type II trans-membrane tyrosine kinase receptor expressed on endothelial cells. By binding to VEGFR2, ramucirumab prevents binding of its ligands (VEGF-A, VEGF-C, and VEGF-D), thereby preventing VEGF-stimulated receptor phosphorylation and downstream ligand-induced proliferation, permeability, and migration of human endothelial cells.

TargetActionsOrganism
AVascular endothelial growth factor receptor 2
antagonist
Humans
Absorption

Not Available

Volume of distribution

5.5 L

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

15 days

Clearance

0.014 L/hour

Adverse Effects
Adverseeffects
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Toxicity

Ramucirumab packaging includes warnings for arterial thromboembolic events, hypertension, infusion-related reactions, gastrointestinal perforation, clinical deterioration in patients with cirrhosis, and reversible posterior leukoencephalopathy syndrome. The most common reactions observed in single-agent-treated patients at a rate of >10% and >2% higher than placebo were hypertension and diarrhea. The most common adverse reactions observed in patients treated with ramucirumab plus paclitaxel at a rate of of >30% and >2% higher than placebo plus paclitaxel were fatigue, neutropenia, diarrhea, and epistaxis.

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 Ramucirumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ramucirumab.
AducanumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ramucirumab.
AlirocumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Alirocumab.
AmivantamabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Anifrolumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Anthrax immune globulin human.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Ramucirumab is combined with Antilymphocyte immunoglobulin (horse).
Interactions
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Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CyramzaSolution10 mg/1mLIntravenousEli Lilly and Company2014-04-21Not applicableUS flag
CyramzaInjection, solution, concentrate10 mg/mlIntravenousEli Lilly Nederland B.V.2020-12-20Not applicableEU flag
CyramzaSolution10 mg/1mLIntravenousEli Lilly and Company2014-04-21Not applicableUS flag
CyramzaInjection, solution, concentrate10 mg/mlIntravenousEli Lilly Nederland B.V.2020-12-20Not applicableEU flag
CyramzaSolution10 mg / mLIntravenousEli Lilly & Co. Ltd.2015-09-10Not applicableCanada flag
CyramzaInjection, solution, concentrate10 mg/mlIntravenousEli Lilly Nederland B.V.2020-12-20Not applicableEU flag

Categories

ATC Codes
L01XC21 — Ramucirumab
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
  • Humans and other mammals

Chemical Identifiers

UNII
D99YVK4L0X
CAS number
947687-13-0

References

Synthesis Reference

http://www.ema.europa.eu/docs/enGB/documentlibrary/EPAR-Publicassessmentreport/human/002829/WC500180726.pdf

General References
  1. Casak SJ, Fashoyin-Aje I, Lemery SJ, Zhang L, Jin R, Li H, Zhao L, Zhao H, Zhang H, Chen H, He K, Dougherty M, Novak R, Kennett S, Khasar S, Helms W, Keegan P, Pazdur R: FDA Approval Summary: Ramucirumab for Gastric Cancer. Clin Cancer Res. 2015 Aug 1;21(15):3372-6. doi: 10.1158/1078-0432.CCR-15-0600. Epub 2015 Jun 5. [Article]
  2. Aprile G, Rijavec E, Fontanella C, Rihawi K, Grossi F: Ramucirumab: preclinical research and clinical development. Onco Targets Ther. 2014 Oct 29;7:1997-2006. doi: 10.2147/OTT.S61132. eCollection 2014. [Article]
  3. Javle M, Smyth EC, Chau I: Ramucirumab: successfully targeting angiogenesis in gastric cancer. Clin Cancer Res. 2014 Dec 1;20(23):5875-81. doi: 10.1158/1078-0432.CCR-14-1071. Epub 2014 Oct 3. [Article]
  4. Aprile G, Bonotto M, Ongaro E, Pozzo C, Giuliani F: Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs. 2013 Dec;73(18):2003-15. doi: 10.1007/s40265-013-0154-8. [Article]
  5. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [Article]
  6. Grothey A, Galanis E: Targeting angiogenesis: progress with anti-VEGF treatment with large molecules. Nat Rev Clin Oncol. 2009 Sep;6(9):507-18. doi: 10.1038/nrclinonc.2009.110. Epub 2009 Jul 28. [Article]
  7. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O'Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol. 2010 Feb 10;28(5):780-7. doi: 10.1200/JCO.2009.23.7537. Epub 2010 Jan 4. [Article]
  8. Lu D, Jimenez X, Zhang H, Bohlen P, Witte L, Zhu Z: Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int J Cancer. 2002 Jan 20;97(3):393-9. [Article]
KEGG Drug
D09371
PubChem Substance
347910183
RxNav
1535922
ChEMBL
CHEMBL1743062
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ramucirumab
FDA label
Download (493 KB)
MSDS
Download (206 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentHepatocellular Carcinoma1
3Active Not RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
3Active Not RecruitingTreatmentTransitional Cell, Carcinoma1
3CompletedTreatmentAdenocarcinoma of the Stomach / Adenocarcinomas of the Gastroesophageal Junction1
3CompletedTreatmentAdenocarcinomas of the Gastroesophageal Junction / Metastatic Gastric Adenocarcinoma1
3CompletedTreatmentAdenocarcinomas / Malignant Neoplasm of Stomach1
3CompletedTreatmentBreast Cancer1
3CompletedTreatmentColorectal Carcinoma (CRC)1
3CompletedTreatmentHepatocellular Carcinoma1
3CompletedTreatmentMalignant Neoplasm of Stomach1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous
Injection, solution, concentrateIntravenous; Parenteral10 MG/ML
SolutionIntravenous10 mg/1mL
SolutionIntravenous10 mg / mL
InjectionParenteral
Injection, solution, concentrateIntravenous
Injection, solution, concentrateIntravenous10 mg/ml
Solution, concentrateIntravenous10 mg
Injection, solution, concentrateIntravenous10 mg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US2013067098No2011-11-022031-11-02US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
Gene Name
KDR
Uniprot ID
P35968
Uniprot Name
Vascular endothelial growth factor receptor 2
Molecular Weight
151525.555 Da
References
  1. Goodkin R, Zaias B, Michelsen WJ: Arteriovenous malformation and glioma: coexistent or sequential? Case report. J Neurosurg. 1990 May;72(5):798-805. [Article]

Drug created on November 18, 2007 18:26 / Updated on October 16, 2021 12:31