Identification

Name
Guselkumab
Accession Number
DB11834
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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.

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
Not Available
External IDs
CNTO1959
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TremfyaSolution100 mgSubcutaneousJanssen Pharmaceuticals2017-11-27Not applicableCanada
TremfyaInjection100 mg/1mLSubcutaneousJanssen Biotech, Inc.2017-07-13Not applicableUs
Categories
UNII
089658A12D
CAS number
1350289-85-8

Pharmacology

Indication

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

Associated Conditions
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
Human
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].

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].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Guselkumab.
AbituzumabThe risk or severity of adverse effects can be increased when Guselkumab is combined with Abituzumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Guselkumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Guselkumab.
AducanumabThe risk or severity of adverse effects can be increased when Guselkumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab 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.
AmatuximabThe risk or severity of adverse effects can be increased when Guselkumab is combined with Amatuximab.
AMG 108The risk or severity of adverse effects can be increased when AMG 108 is combined with Guselkumab.
Food Interactions
Not Available

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. [PubMed:24679469]
  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. [PubMed:24373779]
  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. [PubMed:26201310]
  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. [PubMed:18177599]
External Links
PubChem Substance
347911245
Wikipedia
Guselkumab
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (672 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentPsoriasis2
1Not Yet RecruitingTreatmentAdenomatous Polyposis Coli1
1RecruitingOtherHealthy Volunteers1
2Active Not RecruitingTreatmentPsoriatic Arthritis1
2CompletedTreatmentPalmoplantaris Pustulosis1
2CompletedTreatmentPsoriasis1
3Active Not RecruitingTreatmentPsoriasis4
3Active Not RecruitingTreatmentPsoriatic Arthritis2
3Active Not RecruitingTreatmentPustular Psoriasis1
3CompletedTreatmentPalmoplantar Pustulosis1
3CompletedTreatmentPsoriasis3
3RecruitingTreatmentCrohn's Disease (CD)1
3RecruitingTreatmentPsoriasis1
4Not Yet RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
Not AvailableRecruitingNot AvailablePsoriasis / Psoriatic Arthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous100 mg/1mL
SolutionSubcutaneous100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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. [PubMed:26714681]

Drug created on October 20, 2016 14:52 / Updated on November 14, 2018 12:59