Tralokinumab

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

References:

KEGG DRUG: Tralokinumab [Link]

Download FASTA Format

Synonyms

Tralokinumab

External IDs

CAT-354

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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

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Associated Conditions

Indication Type	Indication	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

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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	antibody	Humans

Absorption

The absolute bioavailability of tralokinumab following subcutaneous administration is 76%, with a median T_max 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

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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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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
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Abciximab	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.

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Adbry	Injection, solution	150 mg/1mL	Subcutaneous	LEO Pharma Inc.	2022-01-02	Not applicable
Adtralza	Injection, solution	300 mg	Subcutaneous	Leo Pharma	2023-11-28	Not applicable
Adtralza	Injection, solution	150 mg	Subcutaneous	Leo Pharma	2021-10-06	Not applicable
Adtralza	Injection, solution	300 mg	Subcutaneous	Leo Pharma	2023-11-28	Not applicable
Adtralza	Injection, solution	150 mg	Subcutaneous	Leo Pharma	2021-10-06	Not applicable

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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Active Not Recruiting	Treatment	Atopic Dermatitis	1
3	Completed	Treatment	Asthma	1
3	Completed	Treatment	Atopic Dermatitis	7
3	Completed	Treatment	Uncontrolled Asthma	2
3	Recruiting	Treatment	Atopic Dermatitis / Atopic Hand Eczema	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Subcutaneous	150 mg/1mL
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

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Details1. Interleukin-13

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antibody

General Function: Interleukin-13 receptor binding
Specific Function: Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.
Gene Name: IL13
Uniprot ID: P35225
Uniprot Name: Interleukin-13
Molecular Weight: 15815.585 Da

References

Health Canada Product Monograph: Adtralza (tralokinumab) for subcutaneous injection [Link]
EMA Summary of Product Characteristics: Adtralza (tralokinumab) for subcutaneous injection [Link]
FDA Approved Drug Products: Adbry (tralokinumab-ldrm) for subcutaneous injection [Link]

Drug created at October 20, 2016 21:31 / Updated at January 31, 2024 01:10

Tralokinumab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References