Dupilumab, sold under the brand name Dupixent, is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

blocking

interleukin 4 The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 ...

and interleukin 13 receptor signalling (IL-4R, IL-13R), used for allergic diseases such as

atopic dermatitis Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin. Atopic dermatitis is also often called simply eczema but the same term is also used to refer to dermatitis, the larger group of skin conditi ...

(eczema),

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

and nasal polyps which result in

chronic sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the Nasal mucosa, mucous membranes that line the Paranasal sinuses, sinuses resulting in symptoms that may include production of thick Mucus#Respiratory system, nasal mucus, nasal conge ...

. It is also used for the treatment of eosinophilic esophagitis, prurigo nodularis and chronic obstructive pulmonary disease. The most common side effects reported by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) include injection site reactions, upper respiratory tract infections, joint pain, and herpes viral infections. The most common side effects reported by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) include injection-site reactions (such as redness, swelling including due to fluid build-up, itching and pain), conjunctivitis (redness and discomfort in the eye) including conjunctivitis due to allergy, joint pain, cold sores, and increased blood levels of a type of white blood cell called eosinophils. It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme. It received approval from the US

(FDA) for moderate-to-severe atopic dermatitis in 2017, and for asthma in 2018. The FDA considers it to be a first-in-class medication. Dupilumab is the first treatment for eosinophilic esophagitis approved by the U.S.

(FDA). Eosinophilic esophagitis is a chronic inflammatory disorder in which eosinophils, a type of white blood cell, are found in the tissue of the esophagus. In adults and adolescents with eosinophilic esophagitis, common symptoms include difficulty swallowing, difficulty eating, and food getting stuck in the esophagus. Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. Dupilumab is the first treatment for prurigo nodularis approved by the FDA. Prurigo nodularis is a rare skin disease that causes hard, itchy lumps (nodules) to form on the skin.

Medical uses

Dupilumab is indicated for the treatment of moderate-to-severe

; moderate-to-severe

; chronic rhinosinusitis with nasal polyps; eosinophilic esophagitis; prurigo nodularis; and chronic obstructive pulmonary disease. It has been shown to be effective at treating aspirin-exacerbated respiratory disease (AERD), a typically difficult to treat condition where aspirin intolerant patients have both CRSwNP and asthma. In May 2022, the indication for dupilumab was updated to include the treatment of eosinophilic esophagitis in people aged twelve years of age and older weighing at least . In September 2022, the indication for dupilumab was updated to include the treatment of adults with prurigo nodularis (PN). In March 2023, the

approved dupilumab for the treatment of severe

in children aged six months to five years who are candidates for

systemic therapy Systemic therapy is a type of psychotherapy that seeks to address people in relationships, dealing with the interactions of groups and their interactional patterns and dynamics. Early forms of systemic therapy were based on cybernetics and syste ...

. In September 2024, the indication for dupilumab was updated to include the treatment of chronic rhinosinusitis with nasal polyps, and chronic obstructive pulmonary disease.

Side effects

Injection site reactions such as redness and pain are common, occurring in approximately 11.4% of cases. Dupilumab can cause allergic reactions,

conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

, and keratitis and, due to its immunosuppressive effects, reactivation of cold sores. In clinical trials, people receiving dupilumab had decreased levels of

T helper cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

Pharmacology

Mechanism of action

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

. Through blockade of IL-4Rα, dupilumab modulates signaling of both the

and interleukin 13 pathways.

Pharmacokinetics

Dupilumab shows a non-linear rate in regard to the target. Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.

History

Regeneron Pharmaceuticals and Sanofi Genzyme jointly developed dupilumab, the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies. Phase II trials for asthma treatment showed increased lung function with increased forced expiratory volume for patients. In October 2016, Regeneron completed a phase III trial comparing dupilumab with topical

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s, in which subjects had a larger decrease in symptoms with both dupilumab and topical steroids than with steroids alone. In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo. The US

(FDA) granted the application for dupilumab priority review designation and in March 2017, the FDA approved dupilumab injection to treat adults with moderate-to-severe eczema. The efficacy and safety of dupilumab in eosinophilic esophagitis was studied in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial, that included two 24-week treatment periods (Part A and Part B) that were conducted independently in separate groups of participants. In Part A and Part B, participants received either placebo or 300 milligrams of dupilumab every week. The two primary measurements of efficacy were the proportion of participants who achieved a certain level of reduced eosinophils in the esophagus at week 24, as determined by assessing participants' esophageal tissue under a microscope, and the change in the participant-reported Dysphagia Symptom Questionnaire (DSQ) score from baseline to week 24. The DSQ is a questionnaire designed to measure difficulty swallowing associated with eosinophilic esophagitis, with total scores ranging from 0 to 84; higher DSQ scores indicate worse symptoms. The efficacy and safety of dupilumab to treat prurigo nodularis among adults were evaluated in two clinical trials, EFC16459 (PRIME) and EFC16460 (PRIME2). Each trial evaluated 300 mg of dupilumab administered every 2 weeks following an initial dose of 600 mg. The treatment lasted for 24 weeks. Effectiveness was mainly assessed by the proportion of subjects whose itchy skin (pruritus) improved by more than four points on the Worst Itch Numeric Rating Scale, the proportion of subjects who achieved score of 0 or 1 on Investigator's Global Assessment PN-stage scale (the equivalent of 0-5 nodules), and the proportion of subjects who achieved a response on both scales at week 24. The FDA granted the application breakthrough therapy designation.

References

{{Authority control Anti-interleukin monoclonal antibodies Sanofi Antiasthmatic drugs