Dupilumab

Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody used for allergic diseases such as eczema (atopic dermatitis), asthma and nasal polyps which result in chronic sinusitis.[1][2][3][4]

Dupilumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL4 receptor alpha
Clinical data
Trade namesDupixent
AHFS/Drugs.comMonograph
MedlinePlusa617021
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx only
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6512H10066N1730O2052S46
Molar mass146898.98 g·mol−1

Side effects include allergic reactions, cold sores, and inflammation of the cornea.[2] It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme.[5][6] It received approval from the United States Food and Drug Administration (FDA) for moderate-to-severe atopic dermatitis in 2017[2] and for asthma in late 2018.[4] The FDA considers it to be a first-in-class medication.[7]

Medical uses

Dupilumab appears to be useful for moderate-to-severe atopic dermatitis for which it is approved in the United States.[8][9] It is also being evaluated for treatment of persistent asthma in adults and adolescents.[9][10] In October 2019, the European Commission (EC) approved Dupixent in chronic rhinosinusitis with nasal polyposis (CRSwNP).[11]


In September 2020, the FDA granted dupilumab breakthrough therapy status for the treatment of eosinophilic esophagitis.[12]

Side effects

Dupilumab can cause several side effects including allergic reactions, conjunctivitis, and keratitis.[2]

There is one reported case of dupilumab triggering hair growth in a patient with complete hair loss.[13] This is being investigated as an unintended, but positive, side effect.

One other case reports a possibility of chronic eosinophilic pneumonia associated with dupixent.[14]

Some concern of potential worsened COVID-19 disease with patients taking dupilumab have been expressed, but according to one study all patients had mild course of disease.[15]

Pharmacology

Mechanism of action

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[16] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways. In clinical trials, specimens from people receiving dupilumab showed decreased levels of Th2 bio-markers.[17]

Pharmacokinetics

Dupilumab shows a non-linear rate in regard to the target.[17] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.[17]

Development

Development of dupilumab was a joint effort by Regeneron Pharmaceuticals and Sanofi, the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies.[18]

The United States Food and Drug Administration granted it priority review status.[19][20] On March 28, 2017, the U.S. Food and Drug Administration approved dupilumab injection to treat adults with moderate-to-severe eczema.[2]

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 duplimab and topical steroids than with steroids alone.[21]

Phase III studies were also performed to evaluate the efficacy of dupilumab in combination with topical corticosteroids. In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo.[17]

Phase II trials for asthma treatment showed increased lung function for patients, showing increased forced expiratory volume.[17]

References
  1. "Statement on a Nonproprietary Name Adopted By The USAN Council - Dupilumab", American Medical Association.
  2. "FDA approves new eczema drug Dupixent". FDA. 2019-09-10.
  3. "FDA approves first treatment for chronic rhinosinusitis with nasal polyps". U.S. Food and Drug Administration (FDA). 26 June 2019. Retrieved 27 June 2019.
  4. "Dupixent- dupilumab injection, solution". DailyMed. 25 June 2020. Retrieved 17 September 2020.
  5. "Sanofi - Commercial collaboration". Sanofi. Retrieved 2017-03-09.
  6. "A powerful research and development engine". www.regeneron.com. Retrieved 2017-03-09.
  7. New Drug Therapy Approvals 2017 (PDF) (Report). U.S. Food and Drug Administration (FDA). January 2018. Retrieved 16 September 2020.
  8. Kraft M, Worm M (April 2017). "Dupilumab in the treatment of moderate-to-severe atopic dermatitis". Expert Review of Clinical Immunology. 13 (4): 301–310. doi:10.1080/1744666X.2017.1292134. PMID 28165826. S2CID 3404484.
  9. Humbert M, Busse W, Hanania NA (January 2018). "Controversies and opportunities in severe asthma". Current Opinion in Pulmonary Medicine. 24 (1): 83–93. doi:10.1097/MCP.0000000000000438. PMID 29059087. S2CID 4433743.
  10. Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. (June 2018). "Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma". The New England Journal of Medicine. 378 (26): 2486–2496. doi:10.1056/nejmoa1804092. PMID 29782217. S2CID 205103217.
  11. "Regeneron reports third quarter 2019". Regeneron Pharmaceuticals, Inc. November 5, 2019.
  12. Inc, Regeneron Pharmaceuticals. "FDA Grants Dupixent® (dupilumab) Breakthrough Therapy Designation for Eosinophilic Esophagitis". www.prnewswire.com. Retrieved 2020-12-01.
  13. Penzi LR, Yasuda M, Manatis-Lornell A, Hagigeorges D, Senna MM (November 2018). "Hair Regrowth in a Patient With Long-standing Alopecia Totalis and Atopic Dermatitis Treated With Dupilumab". JAMA Dermatology. 154 (11): 1358–1360. doi:10.1001/jamadermatol.2018.2976. PMID 30304403.
  14. Menzella, Francesco; Montanari, Gloria; Patricelli, Giulia; Cavazza, Alberto; Galeone, Carla; Ruggiero, Patrizia; Bagnasco, Diego; Facciolongo, Nicola (2019-07-10). "A case of chronic eosinophilic pneumonia in a patient treated with dupilumab". Therapeutics and Clinical Risk Management. 15: 869–875. doi:10.2147/TCRM.S207402. ISSN 1176-6336. PMC 6636310. PMID 31371974.
  15. Thangaraju, Pugazhenthan; Venkatesan, Nanditha; Sudha, T. Y. Sree; Venkatesan, Sajitha; Thangaraju, Eswaran (2020-09-10). "Role of Dupilumab in Approved Indications of COVID-19 Patient: an Efficacy-Based Nonsystematic Critical Analysis". Sn Comprehensive Clinical Medicine: 1–5. doi:10.1007/s42399-020-00510-x. ISSN 2523-8973. PMC 7483051. PMID 32935079.
  16. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. (June 2013). "Dupilumab in persistent asthma with elevated eosinophil levels". The New England Journal of Medicine. 368 (26): 2455–66. doi:10.1056/NEJMoa1304048. PMID 23688323.
  17. Shirley M (July 2017). "Dupilumab: First Global Approval". Drugs. 77 (10): 1115–1121. doi:10.1007/s40265-017-0768-3. PMID 28547386. S2CID 207489287.
  18. "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Retrieved 2017-10-20.
  19. "Novel Biologic Dupilumab Improves Eczema Symptoms". October 2016. Retrieved 30 October 2017.
  20. Walker J (2016-05-30). "New Eczema Treatments Could Be Available Soon". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-05-31.
  21. Hamilton JD, Ungar B, Guttman-Yassky E (2015). "Drug evaluation review: dupilumab in atopic dermatitis". Immunotherapy. 7 (10): 1043–58. doi:10.2217/imt.15.69. PMID 26598956.
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