Tralokinumab
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Identification
- Summary
Tralokinumab is a monoclonal antibody directed against interleukin-13 which is used in the treatment of moderate-to-severe atopic dermatitis in patients requiring systemic therapy.
- Brand Names
- Adbry
- Generic Name
- Tralokinumab
- DrugBank Accession Number
- DB12169
- Background
Atopic dermatitis (AD) is an inflammatory skin disorder that causes skin inflammation, skin barrier dysfunction, and chronic pruritus.4 It is estimated to affect up to 20% of adults and children worldwide, and is frequently associated with other atopic conditions such as asthma or allergic rhinitis. While AD is a heterogenous condition with a variety of apparent genetic and environmental causes,2 it is primarily driven by the pro-inflammatory cytokine interleukin-13 (IL-13).3
Tralokinumab is a fully human IgG4 monoclonal antibody targeted against IL-13. It neutralizes IL-13 activity by inhibiting its ability to bind with receptors, thus helping to alleviate AD symptoms. Tralokinumab was first approved for the treatment of atopic dermatitis by the EMA in June 2021, under the brand name Adtralza (Leo Pharma), and was subsequently approved in Canada in October 2021 and the US in December 2021.6,8
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6374H9822N1698O2014S44
- Protein Average Weight
- 147000.0 Da (Approximate)
- Sequences
>Tralokinumab Heavy chain: QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGLSWVRQAPGQGLEWMGWISANNGDTNY GQEFQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARDSSSSWARWFFDLWGRGTLVTV SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGP SVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQ EGNVFSCSVMHEALHNHYTQKSLSLSLGK
>Tralokinumab Light chain: SYVLTQPPSVSVAPGKTARITCGGNIIGSKLVHWYQQKPGQAPVLVIYDDGDRPSGIPER FSGSNSGNTATLTISRVEAGDEADYYCQVWDTGSDPVVFGGGTKLTVLGQPKAAPSVTLF PPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYL SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
Download FASTA FormatReferences:
- KEGG DRUG: Tralokinumab [Link]
- Synonyms
- Tralokinumab
- External IDs
- CAT-354
Pharmacology
- Indication
Tralokinumab is indicated in Canada, the US, and the EU for the treatment of moderate-to-severe atopic dermatitis in patients who are candidates for systemic therapy and are inadequately controlled with topical interventions.5,8,6 In Canada, tralokinumab is only approved for adults, while in the US and Europe, it is approved for use in patients 12 years of age and older.6,8,5
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Moderate to severe atopic dermatitis •••••••••••• •••••••••• •••••••• •• ••••••• •••••••••• ••••••• •••••••••••• ••••••••• ••• ••• ••••••••• ••••••••• Treatment of Moderate/severe atopic dermatitis •••••••••••• ••••••••••• ••••• ••••••••• ••• •••••••• ••••••• ••••••••• Treatment of Moderate/severe atopic dermatitis •••••••••••• ••••• •••••••••• •••••••• •• ••••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Tralokinumab exerts its therapeutic effects by inhibiting the inflammatory cytokine (IL-13) primarily responsible for the pathogenesis of atopic dermatitis. It is administered subcutaneously with a loading dose of 600mg followed by a maintenance dose of 300mg every two weeks.6 In clinical studies, tralokinumab treatment decreased the concentrations of a number of Th2 and Th22 immunity biomarkers in the blood, including periostin, IL-22, serum IgE. It also reduced epidermal thickness and decreased the expression of Keratin 16 and Ki-67 in skin affected by atopic dermatitis.6
Hypersensitivity reactions, including anaphylaxis, have been reported following the use of tralokinumab.6 Patients experiencing a systemic hypersensitivity reaction should discontinue treatment and initiate immediate therapy as clinically indicated. Tralokinumab should not be used in patients with pre-existing helminth infections, as the influence of tralokinumab on the immune response against helminth infections is unclear.6 Patients with helminth infections should be treated prior to therapy with tralokinumab. Patients becoming infected during the course of therapy may be treated with anti-helminth medications, but should discontinue tralokinumab if the infection fails to resolve.6
- Mechanism of action
Interleukin-13 (IL-13) is a pro-inflammatory cytokine that has been implicated as the primary driver of atopic dermatitis (AD).3 IL-13 binds with high affinity to both a heterodimeric form of IL-13Rα1 - complexed with IL-4Rα - and to IL-13Rα2, both of which are expressed on keratinocytes and fibroblasts.4 While IL-13Rα2 does not appear to act as a signal mediator, the binding of IL-13 to heterodimeric IL-4Rα and IL-13Rα1 activates downstream Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) pathways which proceed to activate various signal transducer and activator of transcription (STAT) pathways.4 STAT signalling induces the expression of periostin, an extracellular matrix protein which serves a number of physiological functions in addition to its pathogenic role in skin fibrosis and chronic allergic inflammation. IL-13 also appears to contribute to skin barrier dysfunction via an indirect downregulation of filaggrin (FLG), a structural protein essential for correct skin barrier functioning.4
Tralokinumab is a monoclonal antibody targeted against IL-13. It neutralizes the activity of IL-13 by blocking its interaction with both the IL-13Rα1/IL-4Rα receptor complex and IL-13Rα2 receptors.6
Target Actions Organism AInterleukin-13 antibodyHumans - Absorption
The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median Tmax of 5-8 days.6 In clinical trials, steady-state serum concentrations were achieved by week 16 of treatment, with trough concentrations ranging from 98.0±41.1 mcg/mL to 101.4±42.7 mcg/mL.6
- Volume of distribution
The volume of distribution of tralokinumab as estimated by population pharmacokinetic analysis was 4.2 L.6
- Protein binding
Little information is available for the protein binding of tralokinumab.
- Metabolism
As with other therapeutic and endogenous proteins, the metabolism of tralokinumab is likely to occur via catabolism to smaller peptides and amino acids and has not been studied directly.6
- Route of elimination
The elimination of tralokinumab occurs through a non-saturable proteolytic pathway.6
- Half-life
The half-life of tralokinumab is approximately 22 days.6
- Clearance
The clearance of tralokinumab following subcutaneous administration was estimated to be 0.149 L/day.5
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
There are no data regarding overdosage with tralokinumab. In clinical trials, intravenous doses up to 30 mg/kg and subcutaneous doses of 600mg every two weeks for 3 months were found to be well-tolerated.5 In the event of a suspected overdose, patients should be administered supportive care as clinically indicated.
- 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 softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Tralokinumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Tralokinumab. Aducanumab The risk or severity of adverse effects can be increased when Tralokinumab is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tralokinumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Tralokinumab. - Food Interactions
- 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 Adbry Injection, solution 300 mg/2mL Subcutaneous Leo Pharma 2024-07-01 Not applicable US Adbry Injection, solution 150 mg/1mL Subcutaneous Leo Pharma 2022-01-02 Not applicable US Adtralza Injection, solution 150 mg Subcutaneous Leo Pharma 2021-10-06 Not applicable EU Adtralza Solution 150 mg / mL Subcutaneous Leo Pharma 2022-03-17 Not applicable Canada Adtralza Injection, solution 300 mg Subcutaneous Leo Pharma 2023-11-28 Not applicable EU
Categories
- ATC Codes
- D11AH07 — Tralokinumab
- 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
- GK1LYB375A
- CAS number
- 1044515-88-9
References
- General References
- Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476. [Article]
- Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, Moate R, van der Merwe R: Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb. J Allergy Clin Immunol. 2019 Jan;143(1):135-141. doi: 10.1016/j.jaci.2018.05.029. Epub 2018 Jun 12. [Article]
- Tsoi LC, Rodriguez E, Degenhardt F, Baurecht H, Wehkamp U, Volks N, Szymczak S, Swindell WR, Sarkar MK, Raja K, Shao S, Patrick M, Gao Y, Uppala R, Perez White BE, Getsios S, Harms PW, Maverakis E, Elder JT, Franke A, Gudjonsson JE, Weidinger S: Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. J Invest Dermatol. 2019 Jul;139(7):1480-1489. doi: 10.1016/j.jid.2018.12.018. Epub 2019 Jan 11. [Article]
- Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, Nakahara T, Furue M: The IL-13-OVOL1-FLG axis in atopic dermatitis. Immunology. 2019 Dec;158(4):281-286. doi: 10.1111/imm.13120. Epub 2019 Oct 1. [Article]
- EMA Summary of Product Characteristics: Adtralza (tralokinumab) for subcutaneous injection [Link]
- Health Canada Product Monograph: Adtralza (tralokinumab) for subcutaneous injection [Link]
- EMA European Public Assessment Report: Adtralza (tralokinumab) [Link]
- FDA Approved Drug Products: Adbry (tralokinumab-ldrm) for subcutaneous injection [Link]
- FDA Approved Drug Products: ADBRY® (tralokinumab-ldrm) injection, for subcutaneous use (December 2023) [Link]
- External Links
- PubChem Substance
- 347911293
- Wikipedia
- Tralokinumab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Atopic Dermatitis 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Atopic Dermatitis / Psoriasis 1 somestatus stop reason just information to hide 4 Recruiting Treatment Atopic Dermatitis 1 somestatus stop reason just information to hide 3 Completed Treatment Asthma 1 somestatus stop reason just information to hide 3 Completed Treatment Atopic Dermatitis 8 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 150 mg/1mL Injection, solution Subcutaneous 300 mg/2mL Injection, solution Subcutaneous 150 MG Injection, solution Subcutaneous 300 mg Solution Subcutaneous 150 mg / mL Solution Subcutaneous 300 mg / 2 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Cytokine that plays important roles in allergic inflammation and immune response to parasite infection (PubMed:8096327, PubMed:8097324). Synergizes with IL2 in regulating interferon-gamma synthesis (PubMed:8096327). Stimulates B-cell proliferation, and activation of eosinophils, basophils, and mast cells (PubMed:7903680, PubMed:8759755). Plays an important role in controlling IL33 activity by modulating the production of transmembrane and soluble forms of interleukin-1 receptor-like 1/IL1RL1 (By similarity). Displays the capacity to antagonize Th1-driven proinflammatory immune response and downregulates synthesis of many proinflammatory cytokines including IL1, IL6, IL10, IL12 and TNF-alpha through a mechanism that partially involves suppression of NF-kappa-B (By similarity). Functions also on nonhematopoietic cells, including endothelial cells where it induces vascular cell adhesion protein 1/VCAM1, which is important in the recruitment of eosinophils (PubMed:8639787). Exerts its biological effects through its receptors which comprises the IL4R chain and the IL13RA1 chain, to activate JAK1 and TYK2, leading to the activation of STAT6 (PubMed:9013879). Aside from IL13RA1, another receptor IL13RA2 acts as a high affinity decoy for IL13 and mediates internalization and depletion of extracellular IL13 (PubMed:21622864)
- Specific Function
- cytokine activity
- Gene Name
- IL13
- Uniprot ID
- P35225
- Uniprot Name
- Interleukin-13
- Molecular Weight
- 15787.535 Da
References
Drug created at October 20, 2016 21:31 / Updated at January 31, 2024 01:10