Lebrikizumab

Identification

Summary

Lebrikizumab is an IgG4 monoclonal antibody against IL-13 used to treat moderate-to-severe atopic dermatitis in adults and adolescents.

Generic Name
Lebrikizumab
DrugBank Accession Number
DB11914
Background

Lebrikizumab is a monoclonal antibody against IL-13 that binds to a different epitope compared tralokinumab.1,2

On November 17, 2023, lebrikizumab was approved by the EMA under the brand name EBGLYSS for the treatment of moderate-to-severe atopic dermatitis in adult and adolescent patients 12 years and older with a body weight of at least 40 kg. This approval is based on the positive results obtained from the Phase 3 studies ADvocate 1 and ADvocate 2, where nearly 80% of patients taking lebrikizumab either as monotherapy or combination therapy with topical corticosteroid achieved skin clearance, itch relief and reduced disease severity by week 16.4

Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
>SUBUNIT_1
QVTLRESGPALVKPTQTLTLTCTVSGFSLSAYSVNWIRQPPGKALEWLAMIWGDGKIVYN
SALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCAGDGYYPYAMDNWGQGSLVTVSSAS
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV
FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_2
QVTLRESGPALVKPTQTLTLTCTVSGFSLSAYSVNWIRQPPGKALEWLAMIWGDGKIVYN
SALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCAGDGYYPYAMDNWGQGSLVTVSSAS
TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFL
FPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRV
VSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQ
VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNV
FSCSVMHEALHNHYTQKSLSLSLGK
>SUBUNIT_3
DIVMTQSPDSLSVSLGERATINCRASKSVDSYGNSFMHWYQQKPGQPPKLLIYLASNLES
GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQNNEDPRTFGGGTKVEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4
DIVMTQSPDSLSVSLGERATINCRASKSVDSYGNSFMHWYQQKPGQPPKLLIYLASNLES
GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQNNEDPRTFGGGTKVEIKRTVAAPSVF
IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS
STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. NIH Inxight: Lebrikizumab [Link]
Download FASTA Format
Synonyms
  • Lebrikizumab
External IDs
  • TNX-650

Pharmacology

Indication

Lebrikizumab is approved by the EMA for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy.3

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofModerate to severe atopic dermatitis••••••••••••••••••••••• ••••••••• •••••• •• •• •• •• ••••• ••••••••• ••• •••••••• •••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

In lebrikizumab clinical studies, lebrikizumab reduced the levels of serum periostin, total immunoglobulin E (IgE), CC chemokine ligand (CCL)17 [thymus and activation-regulated chemokine (TARC)], CCL18 [pulmonary and activation-regulated chemokine (PARC)], and CCL13 [monocyte chemotactic protein-4 (MCP-4)]. The decreases in the type 2 inflammation mediators provide indirect evidence of inhibition of the IL-13 pathway by lebrikizumab.3

Mechanism of action

Lebrikizumab is an immunoglobulin (IgG4) monoclonal antibody that binds with high affinity to interleukin (IL)-13 and selectively inhibits IL-13 signaling through the IL-4 receptor alpha (IL-4Rα)/ IL-13 receptor alpha 1 (IL-13Rα1) heterodimer, thereby inhibiting the downstream effects of IL-13. Inhibition of IL-13 signaling is expected to be of benefit in diseases in which IL-13 is a key contributor to the disease pathogenesis. Lebrikizumab does not prevent the binding of IL-13 to the IL-13 receptor alpha 2 (IL-13Rα2 or decoy receptor), which allows the internalization of IL-13 into the cell.3

TargetActionsOrganism
AInterleukin-13
antibody
Humans
Absorption

After a subcutaneous dose of 250 mg lebrikizumab, peak serum concentrations were achieved approximately 7 to 8 days post-dose.3

Following the 500 mg loading doses at week 0 and week 2, steady-state serum concentrations were achieved with the first 250 mg Q2W dose at week 4.3

Based on a population pharmacokinetic (PK) analysis, the predicted steady-state trough concentrations (Ctrough,ss) following lebrikizumab 250 mg Q2W and Q4W subcutaneous dosing in patients with atopic dermatitis (median and 5th - 95th percentile) were 87 (46-159) µg/mL and 36 (18-68) µg/mL, respectively.3

The absolute bioavailability was estimated at 86% based on a population PK analysis. The injection site location did not significantly influence the absorption of lebrikizumab.3

Volume of distribution

Based on a population PK analysis, the total volume of distribution at steady-state was 5.14 L.3

Protein binding

Little information is available on the protein binding of lebrikizumab.3

Metabolism

Specific metabolism studies were not conducted because lebrikizumab is a protein. Lebrikizumab is expected to degrade to small peptides and individual amino acids via catabolic pathways in the same manner as endogenous IgG.3

Route of elimination

Not Available

Half-life

The mean elimination half-life was approximately 24.5 days.3

Clearance

In the population PK analysis, clearance was 0.154 L/day and was independent of dose.3

Adverse Effects
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Toxicity

There are limited amount of data on the use of lebrikizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of lebrikizumab during pregnancy.3

The mutagenic potential of lebrikizumab has not been evaluated; however monoclonal antibodies are not expected to alter DNA or chromosomes.3

Carcinogenicity studies have not been conducted with lebrikizumab. Evaluation of the available evidence related to IL-13 inhibition and animal toxicology data with lebrikizumab does not suggest carcinogenic potential for lebrikizumab.3

Single intravenous doses up to 10 mg/kg and multiple subcutaneous doses up to 500 mg have been administered to humans in clinical trials without dose-limiting toxicity. There is no specific treatment for lebrikizumab overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment immediately.3

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 Lebrikizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Lebrikizumab.
AducanumabThe risk or severity of adverse effects can be increased when Lebrikizumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Lebrikizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Lebrikizumab.
Food Interactions
No interactions found.

Categories

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
Not Available

Chemical Identifiers

UNII
U9JLP7V031
CAS number
953400-68-5

References

General References
  1. Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taieb A, Owen R, Putnam W, Castro M, DeBusk K, Lin CY, Voulgari A, Yen K, Omachi TA: Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018 May;78(5):863-871.e11. doi: 10.1016/j.jaad.2018.01.017. Epub 2018 Jan 17. [Article]
  2. Prajapati S, Fardos M, Desai AD, Feldman SR: The role of lebrikizumab in the treatment of atopic dermatitis in the adult population. Immunotherapy. 2023 Sep;15(13):981-991. doi: 10.2217/imt-2023-0066. Epub 2023 Jul 4. [Article]
  3. EMA Approved Drug Products: Ebglyss (Lebrikizumab) solution for subcutaneous injection [Link]
  4. Almirall Receives European Commission Approval of EBGLYSS® (lebrikizumab) for Moderate-to-Severe Atopic Dermatitis [Link]
PubChem Substance
347911256
Wikipedia
Lebrikizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAtopic Dermatitis3
3CompletedTreatmentAsthma4
3CompletedTreatmentAtopic Dermatitis5
3CompletedTreatmentAtopic Dermatitis / Dermatitis / Skin Diseases / Skin Diseases, Genetic1
3Not Yet RecruitingTreatmentAtopic Dermatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
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. EMA Approved Drug Products: Ebglyss (Lebrikizumab) solution for subcutaneous injection [Link]

Drug created at October 20, 2016 21:00 / Updated at January 07, 2024 09:46