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:
  1. KEGG DRUG: Tralokinumab [Link]
Download FASTA Format
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 and US, tralokinumab is only approved for adults.6,8 In Europe, it is approved for use in patients 12 years of age and older.5

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Associated Conditions
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

TargetActionsOrganism
AInterleukin-13
antibody
Humans
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

Not Available

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
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
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Tralokinumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Tralokinumab.
AducanumabThe risk or severity of adverse effects can be increased when Tralokinumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tralokinumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Tralokinumab.
AmivantamabThe risk or severity of adverse effects can be increased when Tralokinumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Tralokinumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Tralokinumab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Tralokinumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Tralokinumab.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdbryInjection, solution150 mg/1mLSubcutaneousLEO Pharma Inc.2022-01-02Not applicableUS flag
AdtralzaInjection, solution150 mgSubcutaneousLeo Pharma2021-10-06Not applicableEU flag
AdtralzaInjection, solution150 mgSubcutaneousLeo Pharma2021-10-06Not applicableEU flag
AdtralzaSolution150 mg / mLSubcutaneousLEO Pharma Inc2022-03-17Not applicableCanada flag
AdtralzaInjection, solution150 mgSubcutaneousLeo Pharma2021-10-06Not applicableEU flag

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
  1. Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476. [Article]
  2. 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]
  3. 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]
  4. 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]
  5. EMA Summary of Product Characteristics: Adtralza (tralokinumab) for subcutaneous injection [Link]
  6. Health Canada Product Monograph: Adtralza (tralokinumab) for subcutaneous injection [Link]
  7. EMA European Public Assessment Report: Adtralza (tralokinumab) [Link]
  8. FDA Approved Drug Products: Adbry (tralokinumab-ldrm) for subcutaneous injection [Link]
PubChem Substance
347911293
Wikipedia
Tralokinumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAtopic Dermatitis1
3CompletedTreatmentAsthma1
3CompletedTreatmentAtopic Dermatitis6
3CompletedTreatmentUncontrolled Asthma2
3RecruitingTreatmentAtopic Dermatitis1
3TerminatedTreatmentInadequately Controlled Asthma1
2Active Not RecruitingBasic ScienceAtopic Dermatitis1
2CompletedTreatmentAlopecia Areata (AA)1
2CompletedTreatmentAsthma3
2CompletedTreatmentAtopic Dermatitis2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous150 mg/1mL
Injection, solutionSubcutaneous150 MG
SolutionSubcutaneous150 mg / mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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
  1. Health Canada Product Monograph: Adtralza (tralokinumab) for subcutaneous injection [Link]
  2. EMA Summary of Product Characteristics: Adtralza (tralokinumab) for subcutaneous injection [Link]

Drug created at October 20, 2016 21:31 / Updated at December 01, 2022 23:18