Dupilumab

Identification

Summary

Dupilumab is a monoclonal antibody used to treat moderate to severe atopic dermatitis, asthma, and nasal polyps accompanied by chronic rhinosinusitis in adolescents and adults.

Brand Names

Dupixent

Generic Name

Dupilumab

DrugBank Accession Number

DB12159

Background

Dupilumab is a fully human monoclonal antibody of the immunoglobulin G4 subclass that binds to the interleukin-4 (IL-4) receptor, inhibiting the receptor signaling pathways.³ As an interleukin-4 receptor alpha antagonist, dupilumab inhibits the signaling of pro-inflammatory cytokines, called interleukins (IL), that induce inflammatory and immunological reactions in several atopic or allergic conditions, such as eczema, allergic reaction, and rhinosinusitis.³ Dupilumab was generated by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.⁷

Dupilumab is commonly marketed as Dupixent, which is available as a formulation for subcutaneous injection. It was first approved by the FDA in 2017. It is currently used to treat atopic dermatitis, asthma as an add-on maintenance treatment, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.¹⁴ It is used as monotherapy or in combination with other drugs, such as corticosteroids.^7,8,13 Dupilumab is currently under investigations for potential therapeutic use in diseases driven by allergic reactions or type 2 inflammation, such as pediatric atopic dermatitis, and chronic obstructive pulmonary disease. It is also being studied in combination with another antibody that which targets IL-33.⁹

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Chemical Formula

C₆₅₁₂H₁₀₀₆₆N₁₇₃₀O₂₀₅₂S₄₆

Protein Average Weight

146896.9522 Da

Sequences

>Dupilumab Heavy Chain
EVQLVESGGGLEQPGGSLRLSCAGSGFTFRDYAMTWVRQAPGKGLEWVSSISGSGGNTYY
ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDRLSITIRPRYYGLDVWGQGTT
VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA
VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFL
GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ
FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKS
RWQEGNVFSCSVMHEALHNHYTQKSLSLSLG

>Dupilumab Light Chain
DIVMTQSPLSLPVTPGEPASISCRSSQSLLYSIGYNYLDWYLQKSGQSPQLLIYLGSNRA
SGVPDRFSGSGSGTDFTLKISRVEAEDVGFYYCMQALQTPYTFGQGTKLEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

References:

KEGG DRUG: Dupilumab [Link]

Download FASTA Format

Synonyms

Dupilumab

External IDs

REGN 668
REGN-668
REGN668
SAR 231893
SAR-231893
SAR231893

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

In the US, dupilumab is indicated for the treatment of patients aged six months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.¹⁵ In Europe and Canada, the drug for this indication is approved for patients aged six years and older.^8,13 In Europe, patients six to 11 years of age should have severe atopic dermatitis and be candidates for systemic therapy.⁸ Dupilumab can be used with or without topical corticosteroids for this condition.^7,13

Dupilumab is indicated as an add-on maintenance treatment of patients aged six years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. However, the drug is not indicated for relief of acute bronchospasm or status asthmaticus.^7,8,13

Dupilumab is indicated as an add-on maintenance treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyposis.⁷ In Canada and Europe, it is used with intranasal corticosteroids.^8,13

In the US and Europe, dupilumab is also indicated for the treatment of adults and children aged 12 years and older weighing at least 40 kg with eosinophilic esophagitis (EoE), and adults with prurigo nodularis.^8,14,16

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Approval Level	Age Group	Patient Characteristics	Dose Form
Adjunct therapy in management of	Chronic rhinosinusitis phenotype with nasal polyps (crswnp)	••••••••••••	•••••	•••••••••••• ••••••••••	•••••••••
Adjunct therapy in management of	Chronic rhinosinusitis phenotype with nasal polyps (crswnp)	••••••••••••	•••••	•••••••••• •••••••• •• •••••••• •••••••••••••••• ••••••• •• ••• •• •••••• •• ••• ••• •••• ••••••••	•••••••••
Management of	Eosinophilic esophagitis (eoe)	••••••••••••	••••••••••• •••••	•••• •••••• •• •• ••••• •• ••	•••••••••
Management of	Eosinophilic esophagitis (eoe)	••••••••••••	••••••••••• •••••	•••••••••• ••••••••••• ••••••••• •••••••• •••••• •• •• •• ••••	•••••••••
Adjunct therapy in management of	Moderate to severe asthma	••••••••••••	•••••• •••••••••	•••••••••••• •••••••••	•••••••••

Associated Therapies

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Dupilumab is an recombinant human IgG4 antibody to the IL-4 receptor that works by inhibiting the activation of certain pro-inflammatory cytokines that are implicated in the pathophysiology of several allergic and atopic conditions, including asthma, chronic rhinosinusitis with nasal polyps, and food and environmental allergies. In vivo, dupilumab was shown to reduce the levels of type 2 inflammatory biomarkers associated with atopic dermatitis, such as thymus and activation-regulated chemokine (TARC/CCL17), total serum IgE, allergen-specific IgE, and lactate dehydrogenase (LDH). A decrease in the levels of biomarkers of asthma, such as FeNO, eotaxin-3, IgE, periostin, and eotaxin-3 (CCL26) was also observed.^8,9 Since dupilumab works to suppress the immune response, it is proposed that it may influence the immune response against some infections, such as helminth infections, by inhibiting IL-4/IL-13 signaling. It is advised that infections are appropriately treated until resolved before initiating dupilumab therapy.⁸

While findings of some in vitro and in vivo studies suggest that some cytokine modulators may influence the expression and activity of specific cytochrome P450 (CYP450) enzymes, an open-label drug-drug interaction study demonstrated that dupilumab displays no significant effect on the activity of CYP450 enzymes studied (CYP3A, CYP2C19, CYP2C9, CYP1A2, and CYP2D6).⁵

Mechanism of action

Type 2 inflammatory processes in various allergic and atopic conditions, such as asthma and atopic diseases, involve the type 2 helper T-cell (Th2) immunity.⁴ Upregulation of this Type 2/Th2 pathway is commonly observed in other inflammatory conditions ⁵ and the activation of Th2 cells is linked to the production of Th2-associated cytokines, such as interleukin (IL) 4, IL-5, IL-9, and IL-13.⁴ IL-4 and IL-13 play a central role in inducing inflammatory conditions such as allergic rhinitis, asthma, and atopic dermatitis,⁹ by regulating Type 2 inflammation and immune function. These inflammatory cytokines work by modulating gene expression downstream of receptor signalling,⁵ regulating Th2 cell differentiation, and activating inflammatory cells such as mast cells and macrophages.⁶

There are two types of receptors for IL-4: the type 1 receptor, which is composed of the IL-4 chain (IL-4Rα) and a γ chain (γC), and the type 2 receptor, which is composed of the IL-4Rα chain and the α1 chain of the IL-13 receptor (IL-13Rα1).⁴ Essentially, IL‐4Rα is a component shared by the IL‐4 and IL-13 receptor complexes ³ and is ubiquitously expressed on both innate and adaptive immune cells to promote the signaling of IL-4 and IL-13.⁶ The type I receptor is primarily expressed on lymphocytes and controls Th2-cell differentiation, whereas the type II receptor is mostly found across resident and myeloid cells.¹ Dupilumab is a fully human monoclonal antibody directed against IL‐4Rα to inhibit the signalling of IL‐4 and IL‐13.⁵ Dupilumab inhibits IL-4 signalling via the Type I receptor (IL-4Rα/γc), and both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα).⁸ It ultimately downregulates type-2 immunity.⁴

Target	Actions	Organism
AInterleukin-4 receptor subunit alpha	inhibitor antibody	Humans
AInterleukin-13	inhibitor antibody	Humans
AInterleukin-4	inhibitor antibody	Humans

Absorption

The Cmax following administration of a single subcutaneous dose of 600 mg or 400 mg of dupilumab were 70.1 ± 24.1 mcg/mL or 41.8 ± 12.4 mcg/mL, respectively. The Tmax ranged from 3 to 7 days following administration of a single subcutaneous dose ranging from 75 to 600 mg.⁷ Following a subcutaneous dose, the absolute bioavailability of dupilumab ranged between 61% and 64% in patients with atopic dermatitis or asthma.⁸

In clinical trials, the steady-state concentrations were reached by week 16 following the administration of 600 mg starting dose and 300 mg dose every other week. At these concentrations, the mean trough concentrations ranged from 60.3 ± 35.1 mcg/mL to 79.9 ± 41.4 mcg/mL for 300 mg dose and from 29.2 ± 18.7 to 36.5 ± 22.2 mcg/mL for 200 mg dose administered every other week.⁷

Volume of distribution

The estimated volume of distribution is 4.8 ± 1.3 L.³

Protein binding

There is limited data on the serum protein binding profile of dupilumab.

Metabolism

Being a monoclonal antibody, dupilumab is not expected to undergo significant hepatic metabolism.⁸ While the metabolism of dupilumab has not been characterized, it is speculated that dupilumab undergoes nonspecific degradation into smaller peptides and amino acids, as often observed with endogenous IgG.³

Route of elimination

Being a monoclonal antibody, dupilumab is not expected to undergo significant renal elimination. It is proposed that dupilumab is eliminated via parallel linear and nonlinear pathways. At higher concentrations, dupilumab is primarily cleared through a non-saturable proteolytic pathway. At lower concentrations, it undergoes a non-linear saturable IL-4R α target-mediated elimination.⁸

Half-life

There is limited human data on the half-life of dupilumab.⁸ In single-dose pharmacokinetic studies, the mean half-life of dupilumab following intravenous or subcutaneous administration ranged from 4.8 to 7 days in rats and 11.7 to 20.5 days in cynomolgus monkeys.^11,12 In these studies, the mean half-life was comparable was comparable following intravenous and subcutaneous administration.¹¹

Clearance

There is limited data on the clearance of dupilumab.⁸

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

There is limited data on the overdose of dupilumab. As there is no specific treatment for dupilumab, close monitoring of the patient with appropriate symptomatic treatment is advised in case of suspected overdosage.[]

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
Integrate drug-drug interactions in your software
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Dupilumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Dupilumab.
Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Dupilumab.
Aducanumab	The risk or severity of adverse effects can be increased when Dupilumab is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Dupilumab.

Food Interactions

No interactions found.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Dupixent	Injection, solution	150 mg/ml	Subcutaneous	SANOFI WINTHROP INDUSTRIE	2020-12-16	2023-07-28
Dupixent	Injection, solution	150 mg/ml	Subcutaneous	SANOFI WINTHROP INDUSTRIE	2020-12-16	Not applicable
Dupixent	Solution	300 mg / 2 mL	Subcutaneous	Sanofi Aventis	2021-05-27	Not applicable
Dupixent	Injection, solution	150 mg/ml	Subcutaneous	SANOFI WINTHROP INDUSTRIE	2020-12-16	Not applicable
Dupixent	Injection, solution	150 mg/ml	Subcutaneous	SANOFI WINTHROP INDUSTRIE	2023-11-20	Not applicable

Chemical Identifiers

UNII: 420K487FSG
CAS number: 1190264-60-8

References

General References

Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G: Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21. [Article]
Frampton JE, Blair HA: Dupilumab: A Review in Moderate-to-Severe Atopic Dermatitis. Am J Clin Dermatol. 2018 Aug;19(4):617-624. doi: 10.1007/s40257-018-0370-9. [Article]
D'Ippolito D, Pisano M: Dupilumab (Dupixent): An Interleukin-4 Receptor Antagonist for Atopic Dermatitis. P T. 2018 Sep;43(9):532-535. [Article]
Sastre J, Davila I: Dupilumab: A New Paradigm for the Treatment of Allergic Diseases. J Investig Allergol Clin Immunol. 2018 Jun;28(3):139-150. doi: 10.18176/jiaci.0254. [Article]
Davis JD, Bansal A, Hassman D, Akinlade B, Li M, Li Z, Swanson B, Hamilton JD, DiCioccio AT: Evaluation of Potential Disease-Mediated Drug-Drug Interaction in Patients With Moderate-to-Severe Atopic Dermatitis Receiving Dupilumab. Clin Pharmacol Ther. 2018 Dec;104(6):1146-1154. doi: 10.1002/cpt.1058. Epub 2018 Apr 2. [Article]
Hurdayal R, Brombacher F: Interleukin-4 Receptor Alpha: From Innate to Adaptive Immunity in Murine Models of Cutaneous Leishmaniasis. Front Immunol. 2017 Nov 10;8:1354. doi: 10.3389/fimmu.2017.01354. eCollection 2017. [Article]
FDA Approved Drug Products: Dupixent (dupilumab) for subcutaneous injection [Link]
EMA Approved Drug Products: Dupixent (dupilumab) subcutaneous injection [Link]
Dupixent® (dupilumab) Approved for Severe Asthma by European Commission - Regeneron [Link]
FDA approves first treatment for chronic rhinosinusitis with nasal polyps [Link]
European Medicines Agency: Dupixent (dupilumab) Public Assessment Report [Link]
Australian Public Assessment Report for Dupilumab - TGA [Link]
Health Canada Approved Drug Products: DUPIXENT (dupilumab) subcutaneous injection [Link]
FDA Approved Drug Products: Dupixent (dupilumab) for subcutaneous injection (May 2022) [Link]
FDA Approved Drug Products: DUPIXENT (dupilumab) injection, for subcutaneous use (June 2022) [Link]
FDA Approved Drug Products: DUPIXENT (dupilumab) injection, for subcutaneous use (September 2022) [Link]
FDA approved drug product: DUPIXENT® (dupilumab) injection, for subcutaneous use (Jan 2024) [Link]
FDA Approved Drug Products: DUPIXENT® (dupilumab) injection, for subcutaneous use (Feb 2024) [Link]

External Links

PubChem Substance: 347911292
RxNav: 1876376
Wikipedia: Dupilumab

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
4	Active Not Recruiting	Treatment	Atopic Dermatitis	2
4	Completed	Basic Science	Asthma	1
4	Completed	Basic Science	Atopic Dermatitis	1
4	Completed	Treatment	Asthma	3
4	Completed	Treatment	Atopic Dermatitis	5

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous
Injection, solution	Parenteral; Subcutaneous	100 mg
Injection, solution	Parenteral; Subcutaneous	200 MG
Injection, solution	Parenteral; Subcutaneous	300 MG
Injection, solution	Subcutaneous	100 mg/0.67mL
Injection, solution	Subcutaneous	150 mg/ml
Injection, solution	Subcutaneous	175 mg/ml
Injection, solution	Subcutaneous	200 mg/1.14mL
Injection, solution	Subcutaneous	300 mg/2mL
Solution	Subcutaneous	100 mg / 0.67 mL
Solution	Subcutaneous	200 mg / 1.14 mL
Solution	Subcutaneous	300 mg / 2 mL
Solution	Subcutaneous	300.00 mg
Injection, solution		150 mg/ml
Injection, solution		175 mg/ml
Solution	Subcutaneous	200 mg
Injection, solution	Subcutaneous
Solution	Subcutaneous	300 mg

Prices

Not Available

Patents

Not Available

Properties

State: Not Available
Experimental Properties: Not Available

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Interleukin-4 receptor subunit alpha

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

General Function: Receptor signaling protein activity
Specific Function: Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regu...
Gene Name: IL4R
Uniprot ID: P24394
Uniprot Name: Interleukin-4 receptor subunit alpha
Molecular Weight: 89657.42 Da

References

Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G: Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013 Jun 27;368(26):2455-66. doi: 10.1056/NEJMoa1304048. Epub 2013 May 21. [Article]

Details2. Interleukin-13

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

Agarwal A, Spath D, Sherris DA, Kita H, Ponikau JU: Therapeutic Antibodies for Nasal Polyposis Treatment: Where Are We Headed? Clin Rev Allergy Immunol. 2020 Oct;59(2):141-149. doi: 10.1007/s12016-019-08734-z. [Article]

Details3. Interleukin-4

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

General Function: Interleukin-4 receptor binding
Specific Function: Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-...
Gene Name: IL4
Uniprot ID: P05112
Uniprot Name: Interleukin-4
Molecular Weight: 17492.09 Da

References

Agarwal A, Spath D, Sherris DA, Kita H, Ponikau JU: Therapeutic Antibodies for Nasal Polyposis Treatment: Where Are We Headed? Clin Rev Allergy Immunol. 2020 Oct;59(2):141-149. doi: 10.1007/s12016-019-08734-z. [Article]

Drug created at October 20, 2016 21:30 / Updated at January 31, 2024 01:10

Dupilumab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References

References

References