Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as eczema (atopic dermatitis), asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis and prurigo nodularis.
The most common side effects reported by the US Food and Drug Administration (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 (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 Food and Drug Administration (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. Food and Drug Administration (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 atopic dermatitis, moderate-to-severe asthma, and for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP).
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 EMA approved dupilumab for the treatment of severe atopic dermatitis in children aged six months to five years who are candidates for systemic therapy.
Investigational uses
In March of 2023, Sanofi announced the results of a Phase 3 trial examining the efficacy of dupilumab in the treatment of chronic obstructive pulmonary disease (COPD). In this randomized, double-blind, placebo-controlled trial, dupilumab demonstrated a 30% reduction in moderate or severe acute exacerbations of COPD, as well as significant improvements in lung function and quality of life in people with COPD.
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, and keratitis and, due to its immunosuppressive effects, reactivation of cold sores. In clinical trials, people receiving dupilumab had decreased levels of T helper cells.
Pharmacology
Mechanism of action
Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist. Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 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 corticosteroids, 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.