![]() Dupilumab antigen binding fragment (orange and green) bound to a human IL-4 receptor alpha (purple) | |
Monoclonal antibody | |
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Type | Whole antibody |
Source | Human |
Target | Interleukin 4 (IL4) receptor alpha |
Clinical data | |
Pronunciation | /duˈpɪljumæb/ doo-PIL-yoo-mab |
Trade names | Dupixent |
AHFS/Drugs.com | Monograph |
MedlinePlus | a617021 |
License data | |
Pregnancy category |
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Routes of administration | Subcutaneous |
ATC code | |
Legal status | |
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Identifiers | |
CAS Number | |
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ChemSpider |
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Chemical and physical data | |
Formula | C6512H10066N1730O2052S46 |
Molar mass | 146898.98 g·mol−1 |
Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as atopic dermatitis (eczema), asthma and nasal polyps which result in chronic sinusitis. [6] [7] [8] [4] It is also used for the treatment of eosinophilic esophagitis [9] and prurigo nodularis. [10]
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. [9] 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. [5] It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme. [11] [12] It received approval from the US Food and Drug Administration (FDA) for moderate-to-severe atopic dermatitis in 2017, [7] and for asthma in 2018. [4] The FDA considers it to be a first-in-class medication. [13]
Dupilumab is the first treatment for eosinophilic esophagitis approved by the U.S. Food and Drug Administration (FDA). [9] Eosinophilic esophagitis is a chronic inflammatory disorder in which eosinophils, a type of white blood cell, are found in the tissue of the esophagus. [9] In adults and adolescents with eosinophilic esophagitis, common symptoms include difficulty swallowing, difficulty eating, and food getting stuck in the esophagus. [9] Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. [9] Dupilumab is the first treatment for prurigo nodularis approved by the FDA. [10] Prurigo nodularis is a rare skin disease that causes hard, itchy lumps (nodules) to form on the skin. [10]
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 polyps (CRSwNP). [4] [5] [14] [15] [9] 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. [16] [17]
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 40 kilograms (88 lb). [9]
In September 2022, the indication for dupilumab was updated to include the treatment of adults with prurigo nodularis (PN). [10]
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. [18] [19]
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, [20] 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. [21]
Injection site reactions such as redness and pain are common, occurring in approximately 11.4% of cases. [22] Dupilumab can cause allergic reactions, conjunctivitis, and keratitis and, due to its immunosuppressive effects, reactivation of cold sores. [7] In clinical trials, people receiving dupilumab had decreased levels of T helper cells. [23]
Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist. [24] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways. [23]
Dupilumab shows a non-linear rate in regard to the target. [23] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection. [23]
Regeneron Pharmaceuticals and Sanofi Genzyme jointly developed dupilumab, [25] the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies. [26] Phase II trials for asthma treatment showed increased lung function with increased forced expiratory volume for patients. [23]
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. [27] In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo. [23]
The US Food and Drug Administration (FDA) granted the application for dupilumab priority review designation [28] [29] and in March 2017, the FDA approved dupilumab injection to treat adults with moderate-to-severe eczema. [7]
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. [9] In Part A and Part B, participants received either placebo or 300 milligrams of dupilumab every week. [9] 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. [9] 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. [9]
The efficacy and safety of dupilumab to treat prurigo nodularis among adults were evaluated in two clinical trials, EFC16459 (PRIME) and EFC16460 (PRIME2). [10] Each trial evaluated 300 mg of dupilumab administered every 2 weeks following an initial dose of 600 mg. [10] The treatment lasted for 24 weeks. [10] 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. [10]
Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can vary from small to covering the entire body. Dermatitis is often called eczema, and the difference between those terms is not standardized.
Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Synthélabo merged with Aventis and renamed to Sanofi-Aventis, which were each the product of several previous mergers. It changed its name back to Sanofi in May 2011. The company is a component of the Euro Stoxx 50 stock market index. In 2023, the company’s seat in Forbes Global 2000 was 89.
Atopic dermatitis (AD), also known as atopic eczema, is a long-term type of inflammation of the skin (dermatitis). It results in itchy, red, swollen, and cracked skin. Clear fluid may come from the affected areas, which can thicken over time. AD may also simply be called eczema, a term that generally refers to a larger group of skin conditions.
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate to the esophagus in large numbers. When a trigger food is eaten, the eosinophils contribute to tissue damage and inflammation. Symptoms include swallowing difficulty, food impaction, vomiting, and heartburn.
Prurigo nodularis (PN), also known as nodular prurigo, is a skin disorder characterized by pruritic (itchy), nodular lesions, which commonly appear on the trunk, arms and legs. Patients often present with multiple excoriated nodules caused by chronic scratching. Although the exact cause of PN is unknown, PN is associated with other dermatologic conditions such as untreated or severe atopic dermatitis and systemic causes of pruritus including liver disease and end stage kidney disease. The goal of treatment in PN is to decrease the itch sensation. PN is also known as Hyde prurigo nodularis, or Picker's nodules.
Regeneron Pharmaceuticals, Inc. is an American biotechnology company headquartered in Westchester County, New York. The company was founded in 1988. Originally focused on neurotrophic factors and their regenerative capabilities, giving rise to its name, the company then branched out into the study of both cytokine and tyrosine kinase receptors, which gave rise to their first product, which is a VEGF-trap.
Reslizumab, sold under the brand names Cinqair and Cinqaero, is a humanized monoclonal antibody against human interleukin-5 (IL-5). Reslizumab binds specifically to IL-5, a key cytokine responsible for the differentiation, maturation, recruitment and activation of human eosinophils. By binding to human IL-5, it blocks its biological function; consequently survival and activity of eosinophils are reduced. The benefits with reslizumab are its ability to reduce the exacerbation rate and improve lung function and asthma-related quality of life in patients with severe eosinophilic asthma and with at least one previous asthma exacerbation in the preceding year. The most common side effects are increased blood creatine phosphokinase, myalgia and anaphylactic reactions.
Mepolizumab, sold under the brand name Nucala by GlaxoSmithKline, is a humanized monoclonal antibody used for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis, and hypereosinophilic syndrome (HES). It recognizes and blocks interleukin-5 (IL-5), a signalling protein of the immune system.
Canakinumab, sold under the brand name Ilaris, is a medication for the treatment of systemic juvenile idiopathic arthritis, active Still's disease, including adult-onset Still's disease, gout flares. It is a human monoclonal antibody targeted at interleukin-1 beta. It has no cross-reactivity with other members of the interleukin-1 family, including interleukin-1 alpha.
Lebrikizumab, sold under the brand name Ebglyss is a humanized monoclonal antibody used for the treatment of atopic dermatitis.
Pitrakinra is a 15-kDa human recombinant protein of wild-type human interleukin-4 (IL-4). It is an IL-4 and IL-13 antagonist that has been studied in a phase IIb clinical trial for the treatment of asthma. Two point mutations on pitrakinra confer its ability to block signaling of IL-4 and interleukin-13 (IL-13) by preventing assembly of IL-4 receptor alpha (IL-4Rα) with either IL-2Rγ or IL-13Rα. Upregulation of Th2 cytokines, including IL-4 and IL-13, is thought to be critical for the allergic inflammation associated with atopic diseases such as asthma and eczema. The targets of pitrakinra action are inflammatory cells and structural cells that express IL-4Rα. The drug has been applied both as a subcutaneous injection and as an inhalation, but the latter formulation proved to be more effective.
Benralizumab, sold under the brand name Fasenra, is a monoclonal antibody directed against the alpha chain of the interleukin-5 receptor (CD125). It was developed by MedImmune for the treatment of asthma.
Tralokinumab sold under the brand names Adtralza (EU/UK) and Adbry (US) among others, is a human monoclonal antibody used for the treatment of atopic dermatitis. Tralokinumab targets the cytokine interleukin 13.
Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.
Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.
Crisaborole, sold under the brand name Eucrisa among others, is a nonsteroidal topical medication used for the treatment of mild-to-moderate atopic dermatitis (eczema) in adults and children.
Risankizumab, sold under the brand name Skyrizi, is a humanized monoclonal antibody used for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. It is designed to target interleukin 23A (IL-23A). It is given by subcutaneous injection.
Tezepelumab, sold under the brand name Tezspire, is a human monoclonal antibody used for the treatment of asthma. Tezepelumab blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine that has been suggested to be critical in the initiation and persistence of airway inflammation.
Abrocitinib, sold under the brand name Cibinqo, is a medication used for the treatment of atopic dermatitis (eczema). It is a Janus kinase inhibitor and it was developed by Pfizer. It is taken by mouth.
Type 2 inflammation is a pattern of immune response. Its physiological function is to defend the body against helminths, but a dysregulation of the type 2 inflammatory response has been implicated in the pathophysiology of several diseases.