Abatacept

Identification

Name
Abatacept
Accession Number
DB01281
Description

Abatacept is a soluble fusion protein, which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Structurally, abatacept is a glycosylated fusion protein with a MALDI-MS molecular weight of 92,300 Da and it is a homodimer of two homologous polypeptide chains of 357 amino acids each. It is produced through recombinant DNA technology in mammalian CHO cells. The drug has activity as a selective co-stimulation modulator with inhibitory activity on T lymphocytes. Although approved for the treatment of rheumatoid arthritis, Repligen has entered a slightly different formulation of CTLA4-Ig into clinical trials (RG2077).

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Chemical Formula
C3498H5458N922O1090S32
Protein Average Weight
92300.0 Da (with glycosylation)
Sequences
>Abatacept monomer sequence
MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTF
LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPC
PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED
PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
  • Abatacept recombinant
External IDs
  • BMS-188667
  • CTLA4-IGG4M
  • RG-1046
  • RG-2077
  • RG1046
  • RG2077

Pharmacology

Indication

For the management of the signs and symptoms of moderate-to-severe active rheumatoid arthritis, inducing major clinical response, slowing the progression of structural damage, and improving physical function in adult patients. It is indicated both as a monotherapy and for use in combination with a continued regimen of DMARDs (not including TNF antagonists). Also used for the management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Abatacept is the first in a new class of drugs known as Selective Co-stimulation Modulators. Known as a recombinant fusion protein, the drug consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc portion of human immunoglobulin G1 (IgG1. The Fc portion of the drug consists of the hinge region, the CH2 domain, and the CH3 domain of IgG1. Although there are multiple pathways and cell types involved in the pathogenesis of rheumatoid arthritis, evidence suggests that T-cell activation may play an important role in the immunopathology of the disease. Ordinarily, full T-cell activation requires binding of the T-cell receptor to an antigen-MHC complex on the antigen-presenting cell as well as a co-stimulatory signal provided by the binding of the CD28 protein on the surface of the T-cell with the CD80/86 proteins on the surface of the antigen-presenting cell. CTLA4 is a naturally occurring protein which is expressed on the surface of T-cells some hours or days after full T-cell activation and is capable of binding to CD80/86 on antigen-presenting cells with much greater affinity than CD28. Binding of CTLA4-Ig to CD80/86 provides a negative feedback mechanism which results in T-cell deactivation. Abatacept was developed by Bristol-Myers-Squibb and is licensed in the US for the treatment of Rheumatoid Arthritis in the case of inadequate response to anti-TNF-alpha therapy.

Mechanism of action

Abatacept is a selective costimulation modulator, like CTLA-4, the drug has shown to inhibit T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. Blockade of this interaction has been shown to inhibit the delivery of the second co-stimulatory signal required for optimal activation of T-cells. This results in the inhibition of autoimmune T-Cell activation that has been implcated in the pathogenesis of rheumatoid arthritis.

TargetActionsOrganism
AT-lymphocyte activation antigen CD80
antagonist
Humans
AT-lymphocyte activation antigen CD86
antagonist
Humans
Absorption

When a single 10 mg/kg intravenous infusion of abatacept is administered in healthy subjects, the peak plasma concentration (Cmax) was 292 mcg/mL. When multiple doses of 10 mg/kg was given to rheumatoid arthritis (RA) patients, the Cmax was 295 mcg/mL. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration is 78.6%.

Volume of distribution
  • 0.07 L/kg [RA Patients, IV administration]
  • 0.09 L/kg [Healthy Subjects, IV administration]
  • 0.11 L/kg [RA patients, subcutaneous administration]
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

kidney and liver

Half-life

16.7 (12-23) days in healthy subjects; 13.1 (8-25) days in RA subjects; 14.3 days when subcutaneously administered to adult RA patients.

Clearance
  • 0.23 mL/h/kg [Healthy Subjects after 10 mg/kg Intravenous Infusion]
  • 0.22 mL/h/kg [RA Patients after multiple 10 mg/kg Intravenous Infusions]
  • 0.4 mL/h/kg [juvenile idiopathic arthritis patients]. The mean systemic clearance is 0.28 mL/h/kg when a subcutaneously administered to adult RA patients. The clearance of abatacept increases with increasing body weight.
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea. Doses up to 50 mg/kg have been administered without apparent toxic effect.

Affected organisms
  • Humans and other mammals
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
AbirateroneThe metabolism of Abiraterone can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Abatacept.
AcebutololThe metabolism of Acebutolol can be increased when combined with Abatacept.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Abatacept.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Abatacept.
AcetohexamideThe metabolism of Acetohexamide can be increased when combined with Abatacept.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be increased when combined with Abatacept.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Abatacept.
AdalimumabThe risk or severity of infection can be increased when Adalimumab is combined with Abatacept.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Abatacept.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

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Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
OrenciaInjection, solution50 mg/0.4mLSubcutaneousE.R. Squibb & Sons, L.L.C.2011-07-29Not applicableUS flag
OrenciaPowder, for solution250 mgIntravenousBristol Myers Squibb2006-08-08Not applicableCanada flag
OrenciaInjection, solution125 mg/1mLSubcutaneousE.R. Squibb & Sons, L.L.C.2011-07-29Not applicableUS flag
OrenciaSolution125 mgSubcutaneousBristol Myers SquibbNot applicableNot applicableCanada flag
OrenciaInjection, solution87.5 mg/0.7mLSubcutaneousE.R. Squibb & Sons, L.L.C.2011-07-29Not applicableUS flag
OrenciaInjection, powder, lyophilized, for solution250 mg/15mLIntravenousE.R. Squibb & Sons, L.L.C.2009-01-01Not applicableUS flag
OrenciaSolution125 mgSubcutaneousBristol Myers Squibb2013-05-09Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L04AA24 — Abatacept
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

Chemical Identifiers

UNII
7D0YB67S97
CAS number
332348-12-6

References

Synthesis Reference

Sang-Lin Kim, Hyun-Kwang Tan, Sang-Min Lim, Wuk-Sang Ryu, Hahn-Sun Jung, Song-Jae Lee, Cheon-Ik Park, Seung-Hoon Kang, Dong Il Kim, "Plant Recombinant Human CTLA4IG and a Method for Producing the Same." U.S. Patent US20100189717, issued July 29, 2010.

US20100189717
General References
  1. Dall'Era M, Davis J: CTLA4Ig: a novel inhibitor of costimulation. Lupus. 2004;13(5):372-6. [PubMed:15230295]
  2. Moreland L, Bate G, Kirkpatrick P: Abatacept. Nat Rev Drug Discov. 2006 Mar;5(3):185-6. [PubMed:16557658]
  3. Weisman MH, Durez P, Hallegua D, Aranda R, Becker JC, Nuamah I, Vratsanos G, Zhou Y, Moreland LW: Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthritis. J Rheumatol. 2006 Nov;33(11):2162-6. Epub 2006 Oct 1. [PubMed:17014006]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686]
  5. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318]
  6. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922]
  7. Maxwell L, Singh JA: Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD007277. doi: 10.1002/14651858.CD007277.pub2. [PubMed:19821401]
  8. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998]
  9. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350]
  10. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889]
KEGG Drug
D03203
PubChem Substance
46509198
RxNav
614391
ChEMBL
CHEMBL1201823
Therapeutic Targets Database
DAP000867
PharmGKB
PA164747080
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Abatacept
AHFS Codes
  • 92:36.00 — Disease-modifying Antirheumatic Agents
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (108 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentRheumatoid Arthritis3
4CompletedBasic ScienceRheumatoid Arthritis1
4CompletedTreatmentPrimary Biliary Cholangitis1
4CompletedTreatmentRheumatoid Arthritis5
4Enrolling by InvitationOtherRheumatoid Arthritis1
4Not Yet RecruitingTreatmentPalindromic Rheumatism, Wrist1
4Not Yet RecruitingTreatmentRheumatoid Arthritis2
4RecruitingDiagnosticEvaluate Bone Changes in Patients With PsA1
4RecruitingTreatmentDermatomyositis1
4RecruitingTreatmentMyocardial Inflammation / Rheumatoid Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • Celltrion Inc.
  • E.R. Squibb and Sons LLC
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous250 MG
Injection, powder, lyophilized, for solutionIntravenous250 mg/15mL
Injection, solutionCutaneous; Parenteral125 MG
Injection, solutionCutaneous; Parenteral50 MG
Injection, solutionCutaneous; Parenteral87.5 MG
Injection, solutionSubcutaneous125 mg/1mL
Injection, solutionSubcutaneous50 mg/0.4mL
Injection, solutionSubcutaneous87.5 mg/0.7mL
Injection, solution, concentrateIntravenous250 mg
Injection, powder, lyophilized, for solutionIntravenous262.5 mg
Powder, for solutionIntravenous250 mg
Injection125 mg
SolutionSubcutaneous125 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2110518No2007-05-222012-06-16Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Involved in the costimulatory signal essential for T-lymphocyte activation. T-cell proliferation and cytokine production is induced by the binding of CD28, binding to CTLA-4 has opposite effects an...
Gene Name
CD80
Uniprot ID
P33681
Uniprot Name
T-lymphocyte activation antigen CD80
Molecular Weight
33047.625 Da
References
  1. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [PubMed:16357751]
  2. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686]
  3. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318]
  4. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [PubMed:17020493]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cel...
Gene Name
CD86
Uniprot ID
P42081
Uniprot Name
T-lymphocyte activation antigen CD86
Molecular Weight
37681.97 Da
References
  1. Scheinfeld N: Abatacept: A review of a new biologic agent for refractory rheumatoid arthritis for dermatologists. J Dermatolog Treat. 2006;17(4):229-34. [PubMed:16971318]
  2. Vincenti F, Luggen M: T cell costimulation: a rational target in the therapeutic armamentarium for autoimmune diseases and transplantation. Annu Rev Med. 2007;58:347-58. [PubMed:17020493]
  3. Kremer JM: Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthritis. J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62. [PubMed:16357751]
  4. Weyand CM, Goronzy JJ: T-cell-targeted therapies in rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006 Apr;2(4):201-10. [PubMed:16932686]
  5. Maxwell LJ, Singh JA: Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol. 2010 Feb;37(2):234-45. doi: 10.3899/jrheum.091066. Epub 2010 Jan 15. [PubMed:20080922]
  6. Nogid A, Pham DQ: Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 2006 Nov;28(11):1764-78. [PubMed:17212998]
  7. Hervey PS, Keam SJ: Abatacept. BioDrugs. 2006;20(1):53-61; discussion 62. [PubMed:16573350]
  8. Reynolds J, Shojania K, Marra CA: Abatacept: a novel treatment for moderate-to-severe rheumatoid arthritis. Pharmacotherapy. 2007 Dec;27(12):1693-701. [PubMed:18041889]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 16, 2007 16:55 / Updated on October 21, 2020 01:55

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