Dupilumab

File:Dupixent Pen and Packaging.jpg

Dupilumab is indicated for the treatment of moderate-to-severe atopic dermatitis; moderate-to-severe asthma; chronic rhinosinusitis with nasal polyps; eosinophilic esophagitis; prurigo nodularis; and chronic obstructive pulmonary disease.{{cite journal | vauthors = Kraft M, Worm M | title = Dupilumab in the treatment of moderate-to-severe atopic dermatitis | journal = Expert Review of Clinical Immunology | volume = 13 | issue = 4 | pages = 301–310 | date = April 2017 | pmid = 28165826 | doi = 10.1080/1744666X.2017.1292134 | s2cid = 3404484 }}{{cite journal | vauthors = Humbert M, Busse W, Hanania NA | title = Controversies and opportunities in severe asthma | journal = Current Opinion in Pulmonary Medicine | volume = 24 | issue = 1 | pages = 83–93 | date = January 2018 | pmid = 29059087 | doi = 10.1097/MCP.0000000000000438 | s2cid = 4433743 }} 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.{{cite journal | vauthors = Buchheit KM, Sohail A, Hacker J, Maurer R, Gakpo D, Bensko JC, Taliaferro F, Ordovas-Montanes J, Laidlaw TM | title = Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease | journal = The Journal of Allergy and Clinical Immunology | volume = 150 | issue = 2 | pages = 415–424 | date = August 2022 | pmid = 35460728 | pmc = 9378638 | doi = 10.1016/j.jaci.2022.04.007 }}{{cite journal | vauthors = Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK | title = Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis | journal = The Journal of Allergy and Clinical Immunology | volume = 149 | issue = 4 | pages = 1286–1295 | date = April 2022 | pmid = 34543652 | doi = 10.1016/j.jaci.2021.09.009 | doi-access = free }}

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 {{convert|40|kg|lb}}.{{cite press release | title=FDA Approves First Treatment for Eosinophilic Esophagitis, a Chronic Immune Disorder | website=U.S. Food and Drug Administration (FDA) | date=20 May 2022 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-eosinophilic-esophagitis-chronic-immune-disorder | access-date=20 May 2022 | archive-date=5 August 2022 | archive-url=https://web.archive.org/web/20220805173549/https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-eosinophilic-esophagitis-chronic-immune-disorder | url-status=dead }} {{PD-notice}}{{cite press release | title=FDA Approves Dupixent (dupilumab) as First Treatment for Adults and Children Aged 12 and Older with Eosinophilic Esophagitis | website=Regeneron Pharmaceuticals | date=20 May 2022 | url=https://newsroom.regeneron.com/news-releases/news-release-details/fda-approves-dupixentr-dupilumab-first-treatment-adults-and | access-date=5 April 2025}}

In September 2022, the indication for dupilumab was updated to include the treatment of adults with prurigo nodularis (PN).{{cite web | title=FDA approves first treatment for prurigo nodularis | website=U.S. Food and Drug Administration (FDA) | date=29 September 2022 | url=https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-prurigo-nodularis | access-date=30 September 2022 | archive-date=29 September 2022 | archive-url=https://web.archive.org/web/20220929232434/https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-prurigo-nodularis | url-status=live }} {{PD-notice}}

In March 2023, the European Medicines Agency approved dupilumab for the treatment of severe atopic dermatitis in children aged six months to five years who are candidates for systemic therapy.{{Cite web |date=17 September 2018 |title=Dupixent EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent |access-date=22 March 2023 |website=European Medicines Agency }}{{Cite web | vauthors = Devarasetti H |date=22 March 2023 |title=Sanofi Dupixent receives EC approval for atopic dermatitis |url=https://www.pharmaceutical-technology.com/news/sanof-dupixent-atopic-dermatitis/ |access-date=22 March 2023 |website=Pharmaceutical Technology }}

In September 2024, the indication for dupilumab was updated to include the treatment of chronic rhinosinusitis with nasal polyps,{{cite press release | title=Dupixent (dupilumab) Approved in the U.S. as First and Only Treatment for Adolescents with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) | website=Regeneron Pharmaceuticals | date=13 September 2024 | url=https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-approved-us-first-and-only-treatment | access-date=5 April 2025}} and chronic obstructive pulmonary disease.{{cite press release | title=Dupixent approved in the US as the first-ever biologic medicine for patients with COPD | website=Sanofi | date=27 September 2024 | url=https://www.news.sanofi.us/2024-09-27-Dupixent-approved-in-the-US-as-the-first-ever-biologic-medicine-for-patients-with-COPD | access-date=5 April 2025}}

Injection site reactions such as redness and pain are common, occurring in approximately 11.4% of cases.{{cite journal | vauthors = Kim PJ, Lansang RP, Vender R | title = A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections | journal = Journal of Cutaneous Medicine and Surgery | volume = 27 | issue = 4 | pages = 358–367 | date = July 2023 | pmid = 37533141 | doi = 10.1177/12034754231188444 | doi-access = free | pmc = 10486173 }} 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.

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.{{cite journal | vauthors = 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 | title = Dupilumab in persistent asthma with elevated eosinophil levels | journal = The New England Journal of Medicine | volume = 368 | issue = 26 | pages = 2455–66 | date = June 2013 | pmid = 23688323 | doi = 10.1056/NEJMoa1304048 | doi-access = free }} Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways.{{cite journal | vauthors = Shirley M | title = Dupilumab: First Global Approval | journal = Drugs | volume = 77 | issue = 10 | pages = 1115–1121 | date = July 2017 | pmid = 28547386 | doi = 10.1007/s40265-017-0768-3 | s2cid = 207489287 }}

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.

Regeneron Pharmaceuticals and Sanofi Genzyme jointly developed dupilumab,{{Cite web | vauthors = Spencer D | date = 8 March 2020 | work = Pharmaboardroom |url= https://pharmaboardroom.com/articles/sanofis-dupixent-soaring-in-2020/|title=Sanofi Genzyme Head on Incredible Success of "Once-in-a-Career" Product Dupixent|access-date=18 May 2021|archive-date=18 May 2021|archive-url=https://web.archive.org/web/20210518051828/https://pharmaboardroom.com/articles/sanofis-dupixent-soaring-in-2020/|url-status=live}} the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies.{{Cite web|url=https://www.sec.gov/Archives/edgar/data/872589/000153217617000027/regn-063017x10q.htm|title=SEC 10-Q Filing of Regeneron|date=30 June 2017|website=SEC.gov|access-date=20 October 2017|archive-date=21 October 2017|archive-url=https://web.archive.org/web/20171021004232/https://www.sec.gov/Archives/edgar/data/872589/000153217617000027/regn-063017x10q.htm|url-status=live}} 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.{{cite journal | vauthors = Hamilton JD, Ungar B, Guttman-Yassky E | title = Drug evaluation review: dupilumab in atopic dermatitis | journal = Immunotherapy | volume = 7 | issue = 10 | pages = 1043–58 | date = 2015 | pmid = 26598956 | doi = 10.2217/imt.15.69 }} 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 Food and Drug Administration (FDA) granted the application for dupilumab priority review designation{{cite web |title=Novel Biologic Dupilumab Improves Eczema Symptoms |url=http://www.medpagetoday.com/MeetingCoverage/EADV/60571 |access-date=30 October 2017 |date=October 2016 |archive-date=11 March 2017 |archive-url=https://web.archive.org/web/20170311230215/http://www.medpagetoday.com/MeetingCoverage/EADV/60571 |url-status=live }}{{Cite news|url=https://www.wsj.com/articles/new-eczema-treatments-could-be-available-soon-1464637182|title=New Eczema Treatments Could Be Available Soon| vauthors = Walker J |date=30 May 2016|newspaper=The Wall Street Journal|issn=0099-9660|access-date=31 May 2016|archive-date=5 January 2018|archive-url=https://web.archive.org/web/20180105050332/https://www.wsj.com/articles/new-eczema-treatments-could-be-available-soon-1464637182|url-status=live}} 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.{{cite web | title=CY 2024 CDER Breakthrough Therapy Calendar Year Approvals | url=https://www.fda.gov/media/97001/download | format=PDF | publisher=U.S. Food and Drug Administration (FDA) | date=30 September 2024 }}

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