Guselkumab

Identification

Summary

Guselkumab is a monoclonal antibody used to treat moderate to severe plaque psoriasis.

Brand Names
Tremfya
Generic Name
Guselkumab
DrugBank Accession Number
DB11834
Background

Guselkumab is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that selectively blocks interleukin-23. IL-23 is an inflammatory cytokine that activates the CD4+ T-helper (Th17) cell pathway to mediate the inflammatory cascade that induces psoriatic plaque formation 2. In clinical trials, guselkumab demonstrated improved skin clearance and symptomatic improvements in dermatological manifestations of psoriasis.

Developed by Janssen, the subcutenous injection form of guselkumab was approved in July 2017 under the market name Tremfya for the treatment of adult patients with moderate-to-severe plaque psoriasis.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6402H9864N1676O1994S42
Protein Average Weight
143.6 Da (units in kg/mol)
Sequences
>Heavy chain
EVQLVQSGAEVKKPGESLKISCKGSGYSFSNYWIGWVRQMPGKGLEWMGIIDPSNSYTRY
SPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARWYYKPFDVWGQGTLVTVSSAST
KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY
SLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSV
FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY
RVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK
NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG
NVFSCSVMHEALHNHYTQKSLSLSPGK
>Light chain
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGSGYDVHWYQQLPGTAPKLLIYGNSKRPSGV
PDRFSGSKSGTSASLAITGLQSEDEADYYCASWTDGLSLVVFGGGTKLTVLGQPKAAPSV
TLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAAS
SYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
Download FASTA Format
Synonyms
  • Guselkumab
External IDs
  • CNTO1959

Pharmacology

Indication

Indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Guselkumab is shown to reduce serum levels of IL-17A, IL-17F and IL-22 Label.

Mechanism of action

Guselkumab targets the p19 alpha subunit of IL-23. While IL-23 promotes the normal inflammatory and immune responses, the p19 and p40 subunits of IL-23 are found to be over-expressed in the condition of psoriasis and other autoimmune inflammatory skin diseases 2,4. Guselkumab selectively binds to the p19 subunit of IL-23 in dendritic cells and keratinocytes and blocks its interaction with IL-23 receptor, which further prevents the release of other pro-inflammatory cytokines and chemokines via stimulation of immune cells such as Th17 cells Label. Thus, guselkumab blocks the abnormally-heightened signalling of inflammatory cascades that promote epidermal abnormalities including keratinocyte hyperproliferation and psoriatic plaque formation 3.

TargetActionsOrganism
AInterleukin-23 subunit alpha
blocker
Humans
Absorption

Following a 100mg subcutaneous administration, the peak plasma concentration (Cmax) of guselkumab is 8.09 ± 3.68 mcg/mL which is reached after approximately 5.5 days Label.

Volume of distribution

The apparent volume of distribution is 13.5 L Label.

Protein binding

Not Available

Metabolism

Like other human IgG monoclonal antibodies, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways Label.

Route of elimination

Like other human IgG monoclonal antibodies, guselkumab is expected to be both renally and fecally excreted as smaller peptide units.

Half-life

Mean half-life of guselkumab is approximately 15 to 18 days in subjects with plaque psoriasis Label.

Clearance

Apparent clearance in subjects with plaque psoriasis is 0.516 L/day Label.

Adverse Effects
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Toxicity

Animal studies to assess the effect of guselkumab on carcinogenesis, mutagenesis and impairment on fertility have not been conducted. When subcutaneously injected into guinea pigs, the doses of guselkumab up to 100mg/kg twice-weekly demonstrated no effects on fertility parameters Label.

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
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Guselkumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Guselkumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Guselkumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Guselkumab.
AducanumabThe risk or severity of adverse effects can be increased when Guselkumab is combined with Aducanumab.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Guselkumab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Guselkumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Guselkumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Guselkumab.
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Guselkumab.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TremfyaInjection, solution100 mgSubcutaneousJanssen Cilag International Nv2020-12-16Not applicableEU flag
TremfyaSolution100 mg / 1 mLSubcutaneousJanssen Pharmaceuticals2017-11-27Not applicableCanada flag
TremfyaInjection, solution100 mgSubcutaneousJanssen Cilag International Nv2020-12-16Not applicableEU flag
TremfyaInjection, solution100 mgSubcutaneousJanssen Cilag International Nv2020-12-16Not applicableEU flag
TremfyaInjection, solution100 mgSubcutaneousJanssen Cilag International Nv2020-12-16Not applicableEU flag
TremfyaInjection100 mg/1mLSubcutaneousJanssen Biotech, Inc.2017-07-13Not applicableUS flag
Tremfya One-pressSolution100 mg / 1 mLSubcutaneousJanssen Pharmaceuticals2019-05-20Not applicableCanada flag

Categories

ATC Codes
L04AC16 — Guselkumab
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
089658A12D
CAS number
1350289-85-8

References

General References
  1. Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, Li K, Campbell K, Marciniak SJ Jr, Wasfi Y, Wang Y, Szapary P, Krueger JG: Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014 Apr;133(4):1032-40. doi: 10.1016/j.jaci.2014.01.025. [Article]
  2. Levin AA, Gottlieb AB: Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014 Mar;70(3):555-61. doi: 10.1016/j.jaad.2013.10.043. Epub 2013 Dec 24. [Article]
  3. Gaspari AA, Tyring S: New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors. Dermatol Ther. 2015 Jul-Aug;28(4):179-93. doi: 10.1111/dth.12251. [Article]
  4. Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A: Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep. 2007 Dec;9(6):461-7. [Article]
PubChem Substance
347911245
RxNav
1928588
Wikipedia
Guselkumab
FDA label
Download (672 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
4Not Yet RecruitingTreatmentPsoriasis1
4Not Yet RecruitingTreatmentPsoriatic Arthritis1
4RecruitingTreatmentPsoriasis Guttate / Psoriasis Vulgaris (Plaque Psoriasis)1
4RecruitingTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)2
3Active Not RecruitingTreatmentPsoriasis2
3CompletedTreatmentPalmoplantar Pustulosis1
3CompletedTreatmentPsoriasis7
3CompletedTreatmentPsoriatic Arthritis3
3CompletedTreatmentPustular Psoriasis (PP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous
InjectionSubcutaneous100 mg/1mL
Injection, solutionParenteral
Injection, solutionParenteral; Subcutaneous
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous100 mg
Injection, solutionSubcutaneous100 mg/ml
SolutionSubcutaneous100 mg / 1 mL
SolutionSubcutaneous100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Blocker
General Function
Not Available
Specific Function
Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peri...
Gene Name
IL23A
Uniprot ID
Q9NPF7
Uniprot Name
Interleukin-23 subunit alpha
Molecular Weight
20729.56 Da
References
  1. Campa M, Mansouri B, Warren R, Menter A: A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis. Dermatol Ther (Heidelb). 2016 Mar;6(1):1-12. doi: 10.1007/s13555-015-0092-3. Epub 2015 Dec 29. [Article]

Drug created on October 20, 2016 20:52 / Updated on July 24, 2021 14:58