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.
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- Contraindications & Blackbox Warnings
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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.
Target Actions Organism AInterleukin-23 subunit alpha blockerHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Guselkumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Guselkumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Guselkumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Guselkumab. Aducanumab The risk or severity of adverse effects can be increased when Guselkumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Guselkumab. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Guselkumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Guselkumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Guselkumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Guselkumab. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tremfya Injection, solution 100 mg Subcutaneous Janssen Cilag International Nv 2020-12-16 Not applicable EU 
Tremfya Solution 100 mg / 1 mL Subcutaneous Janssen Pharmaceuticals 2017-11-27 Not applicable Canada 
Tremfya Injection, solution 100 mg Subcutaneous Janssen Cilag International Nv 2020-12-16 Not applicable EU Tremfya Injection, solution 100 mg Subcutaneous Janssen Cilag International Nv 2020-12-16 Not applicable EU Tremfya Injection 100 mg/1mL Subcutaneous Janssen Biotech, Inc. 2017-07-13 Not applicable US 
Tremfya Injection, solution 100 mg Subcutaneous Janssen Cilag International Nv 2020-12-16 Not applicable EU Tremfya One-press Solution 100 mg / 1 mL Subcutaneous Janssen Pharmaceuticals 2019-05-20 Not applicable Canada
Categories
- ATC Codes
- L04AC16 — Guselkumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Interleukin Inhibitors
- Interleukin-23 Antagonist
- Interleukin-23 Subunit p19
- Misc. Skin and Mucous Membrane Agents
- Proteins
- Serum Globulins
- 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
- 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]
- 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]
- 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]
- 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]
- External Links
- PubChem Substance
- 347911245
- 1928588
- Wikipedia
- Guselkumab
- FDA label
- Download (672 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Psoriasis (PsO) 1 4 Completed Treatment Psoriasis (PsO) / Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Completed Treatment Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Recruiting Treatment Psoriasis (PsO) 3 4 Recruiting Treatment Psoriasis (PsO) / Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Recruiting Treatment Psoriasis Guttate / Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Recruiting Treatment Psoriatic Arthritis 1 3 Active Not Recruiting Treatment Crohn's Disease (CD) 1 3 Active Not Recruiting Treatment Psoriasis (PsO) 1 3 Completed Treatment Palmoplantar Pustulosis (PPP) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous Injection Subcutaneous 100 mg/1mL Injection, solution Parenteral 100 MG Injection, solution Parenteral; Subcutaneous 100 MG Injection, solution Subcutaneous 100 MG Injection, solution Subcutaneous 100 mg/ml Solution Subcutaneous 100 mg / 1 mL Injection, solution 100 mg/ml Injection, solution Subcutaneous Solution Subcutaneous 100 mg/ml Solution Subcutaneous 100 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- 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
- 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 at October 20, 2016 20:52 / Updated at June 03, 2022 07:24