Ipilimumab

Identification

Summary

Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody used to treat metastatic or unresectable melanoma.

Brand Names
Yervoy
Generic Name
Ipilimumab
DrugBank Accession Number
DB06186
Background

Ipilimumab is a fully humanized IgG1 monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4 (CTLA-4).5 Blocking CTLA-4 removes an inhibitory signal from reducing the activity of T lymphocytes.1,2,5 Ipilimumab was developed by Bristol-Myers Squibb and Medarex.5

Ipilimumab was granted FDA approval on 25 March 2011.5

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db06186
Protein Chemical Formula
C6572H10126N1734O2080S40
Protein Average Weight
148000.0 Da
Sequences
>Ipilimumab heavy chain (patent appl. US20150283234) 
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYTMHWVRQAPGKGLEWVTFISYDGNNKYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAIYYCARTGWLGPFDYWGQGTLVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>Ipilimumab light chain 
EIVLTQSPGTLSLSPGERATLSCRASQSVGSSYLAWYQQKPGQAPRLLIYGAFSRATGIP
DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKVEIKRTVAAPSVFIFP
PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • Ipilimumab
External IDs
  • BMS-734016
  • MDX-010
  • MDX-101
  • MDX-CTLA-4
  • MOAB-CTLA-4

Pharmacology

Indication

Ipilimumab is indicated to treat unresectable or metastatic melanoma, as an adjuvant in the treatment of cutaneous melanoma, to treat microsatellite-high or mismatch repair deficient metastatic colorectal cancer, or to treat hepatocellular carcinoma.5 Ipilimumab with nivolumab is indicated to treat advanced renal cell carcinoma.5

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Ipilimumab is a human IgG1 that binds CTLA-4, preventing 1 T-cell inhibition signal pathway.3 It has a long duration of action as it is given every 3 to 4 weeks.5 Patients should be counselled regarding the risk of immune-mediated adverse effects, infusion related reactions, and embryo-fetal toxicity.5

Mechanism of action

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that competes with the stimulatory CD28 for binding to B7 on antigen presenting cells.3 CTLA-4 and CD28 are both presented on the surface of T-cells.3 Ipilimumab is a human IgG1 that binds CTLA-4, preventing the inhibition of T-cell mediated immune responses to tumors.3

TargetActionsOrganism
ACytotoxic T-lymphocyte protein 4
inhibitor
antibody
Humans
Absorption

Cmax was 65.8µg/mL for 2-6 year olds, 70.1µg/mL for 6-<12 year olds, and 73.3µg/mL in patients 12 years and older.5 Data regarding the AUC and Tmax of ipilumumab are not readily available.3,5

Volume of distribution

The volume of distribution at steady-state of ipilimumab is 7.21L.3

Protein binding

Data regarding the protein binding of ipilimumab is not readily available.5

Metabolism

The metabolism of ipilimumab does not involve the cytochrome P450 enzyme system.5,6 Because ipilimumab is a protein, it is expected to be degraded into small peptides and amino acids by proteolytic enzymes.4

Route of elimination

Data regarding the route of elimination of ipilimumab is not readily available.5

Half-life

Ipilimumab has a half life of 14.7 days.3

Clearance

Ipilimumab has a clearance of 15.3 mL/hr.3 Systemic clearance increases proportionally with body weight.6

Adverse Effects
Adverseeffects
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Toxicity

Data regarding ipilumumab overdose is not readily available.5 However, the most common adverse reactions to ipilumumab are fatigue, diarrhea, pruritus, rash, and colitis.5

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
AbacavirAbacavir may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ipilimumab.
AceclofenacAceclofenac may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Ipilimumab which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
AclidiniumIpilimumab may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineIpilimumab may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Ipilimumab which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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International/Other Brands
Yervoy
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
YervoyInjection5 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2011-03-25Not applicableUS flag
YervoyInjection, solution, concentrate5 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2020-12-22Not applicableEU flag
YervoyInjection5 mg/1mLIntravenousBaxter Pharmaceutical Solutions, LLC2011-03-252016-04-11US flag
YervoyLiquid5 mg / mLIntravenousBristol Myers Squibb2012-03-08Not applicableCanada flag
YervoyInjection5 mg/1mLIntravenousE.R. Squibb & Sons, L.L.C.2011-03-25Not applicableUS flag
YervoyInjection5 mg/1mLIntravenousBaxter Pharmaceutical Solutions, LLC2011-03-252016-04-11US flag
YervoyInjection, solution, concentrate5 mg/mlIntravenousBristol Myers Squibb Pharma Eeig2020-12-22Not applicableEU flag

Categories

ATC Codes
L01XC11 — Ipilimumab
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
6T8C155666
CAS number
477202-00-9

References

General References
  1. Johnson DB, Peng C, Abramson RG, Ye F, Zhao S, Wolchok JD, Sosman JA, Carvajal RD, Ariyan CE: Clinical Activity of Ipilimumab in Acral Melanoma: A Retrospective Review. Oncologist. 2015 Jun;20(6):648-52. doi: 10.1634/theoncologist.2014-0468. Epub 2015 May 11. [Article]
  2. Thumar JR, Kluger HM: Ipilimumab: a promising immunotherapy for melanoma. Oncology (Williston Park). 2010 Dec;24(14):1280-8. [Article]
  3. Trinh VA, Hagen B: Ipilimumab for advanced melanoma: a pharmacologic perspective. J Oncol Pharm Pract. 2013 Sep;19(3):195-201. doi: 10.1177/1078155212459100. Epub 2012 Oct 9. [Article]
  4. Fellner C: Ipilimumab (yervoy) prolongs survival in advanced melanoma: serious side effects and a hefty price tag may limit its use. P T. 2012 Sep;37(9):503-30. [Article]
  5. FDA Approved Drug Products: Yervoy Ipilimumab Intravenous Injection [Link]
  6. BC Cancer Agency: Yervoy Monograph [Link]
KEGG Drug
D04603
PubChem Substance
347910341
RxNav
1094833
ChEMBL
CHEMBL1789844
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ipilimumab
FDA label
Download (1.13 MB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentLung Cancers1
4Active Not RecruitingTreatmentMelanoma, Malignant1
4Active Not RecruitingTreatmentRenal Cell Adenocarcinoma1
4Not Yet RecruitingTreatmentRenal Cancers1
4TerminatedTreatmentMetastatic Melanoma1
3Active Not RecruitingTreatmentAdvanced Non Small Cell Lung Cancer (NSCLC)1
3Active Not RecruitingTreatmentAdvanced Renal Cell Carcinoma (aRCC) / Metastatic Renal Cell Carcinoma ( mRCC)1
3Active Not RecruitingTreatmentGastro Esophageal Junction Cancer / Malignant Neoplasm of Stomach1
3Active Not RecruitingTreatmentHead and Neck Carcinoma2
3Active Not RecruitingTreatmentHepatocellular Carcinoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous5 mg/1mL
Injection, solution, concentrateIntravenous5 mg/ml
Injection, solution, concentrateIntravenous; Parenteral5 MG/ML
LiquidIntravenous5 mg / mL
Injection, solution, concentrateIntravenous
Injection, solution, concentrateIntravenous drip5 g
SolutionIntravenous50 mg
SolutionIntravenous5 mg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2381770No2007-08-072020-08-08Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)80-90 ºC (based on IgG properties)McConnell A., et al. (2014). MAbs. Sep-Oct; 6 (5); 1274-1282
boiling point (°C)Fab and Fc domains denaturates at 60 and 70 ºC respectivelyArnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404
water solubility50 mg/mlHuman IgG purified. Product Information
isoelectric point6.1-8.5 Agrisera Information about IgG antibodies.

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Antibody
General Function
Not Available
Specific Function
Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of t...
Gene Name
CTLA4
Uniprot ID
P16410
Uniprot Name
Cytotoxic T-lymphocyte protein 4
Molecular Weight
24655.63 Da
References
  1. Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, Suri KB, Levy C, Allen T, Mavroukakis S, Lowy I, White DE, Rosenberg SA: Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother. 2007 Nov-Dec;30(8):825-30. [Article]

Drug created on March 19, 2008 16:16 / Updated on October 24, 2021 16:00