Dupilumab

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

Dupilumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL4 receptor alpha
Clinical data
Trade namesDupixent
Routes of
administration		Injection
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6512H10066N1730O2052S46
Molar mass146.9 kg/mol 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.[4][5] It received approval from the United States Food and Drug Administration for moderate-to-severe atopic dermatitis in 2017.[2] As of 2019 it costs about US$46,000 per year.[6]

Medical uses

Dupilumab appears to be useful for moderate-to-severe atopic dermatitis for which it is approved in the United States.[7][8] It is also being evaluated for treatment of persistent asthma in adults and adolescents.[8][9] In October 2019, the European Commission (EC) approved Dupixent in chronic rhinosinusitis with nasal polyposis (CRSwNP)[10].

Side effects

Dupilumab causes 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.[11] This is being investigated as an unintended, but positive side effect.

Pharmacology

Mechanism of action

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[12] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways. In clinical trials, patients saw decreased levels of Th2 bio-markers.[13]

Pharmacokinetics

Dupilumab shows a non-linear rate in regard to the target.[13] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.[13]

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.[14]

The United States Food and Drug Administration granted it priority review status.[15][16] 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.[17]

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.[13]

Phase II trials for asthma treatment showed increased lung function for patients, showing increased levels of forced expiratory volume.[13]

References
  1. "Statement On A Nonproprietary Name Adopted By The USAN Council - Dupilumab", American Medical Association.
  2. "FDA approves new eczema drug Dupixent". FDA.
  3. "FDA approves first treatment for chronic rhinosinusitis with nasal polyps". FDA. 26 June 2019. Retrieved 27 June 2019.
  4. "Sanofi - Commercial collaboration". Sanofi. Retrieved 2017-03-09.
  5. "A powerful research and development engine". www.regeneron.com. Retrieved 2017-03-09.
  6. Thomas, Katie (28 March 2017). "Severe Eczema Drug Is Approved by F.D.A.; Price Tag Is $37,000 a Year". The New York Times. Retrieved 30 March 2017.
  7. 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.
  8. Humbert, M; Busse, W; Hanania, NA (20 October 2017). "Controversies and opportunities in severe asthma". Current Opinion in Pulmonary Medicine. 24 (1): 83–93. doi:10.1097/MCP.0000000000000438. PMID 29059087.
  9. Castro, Mario; Corren, Jonathan; Pavord, Ian D.; et al. (2018-06-28). "Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma". New England Journal of Medicine. 378 (26): 2486–2496. doi:10.1056/nejmoa1804092. ISSN 0028-4793. PMID 29782217.
  10. Regeneron reports third quarter 2019: https://investor.regeneron.com/news-releases/news-release-details/regeneron-reports-third-quarter-2019-financial-and-operating
  11. Penzi, Lauren R.; Yasuda, Mariko; Manatis-Lornell, Athena; Hagigeorges, Dina; Senna, Maryanne M. (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.
  12. Wenzel, Sally; Ford, Linda; Pearlman, David; et al. (2013). "Dupilumab in Persistent Asthma with Elevated Eosinophil Levels". New England Journal of Medicine. 368 (26): 2455–2466. doi:10.1056/NEJMoa1304048. PMID 23688323.
  13. Shirley, Matt (2017-07-01). "Dupilumab: First Global Approval". Drugs. 77 (10): 1115–1121. doi:10.1007/s40265-017-0768-3. ISSN 0012-6667. PMID 28547386.
  14. "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Retrieved 2017-10-20.
  15. "Novel Biologic Dupilumab Improves Eczema Symptoms". Retrieved 30 October 2017.
  16. Walker, Joseph (2016-05-30). "New Eczema Treatments Could Be Available Soon". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-05-31.
  17. Hamilton, Jennifer D.; Ungar, Benjamin; Guttman-Yassky, Emma (2015). "Drug evaluation review: dupilumab in atopic dermatitis". Immunotherapy. 7 (10): 1043–1058. doi:10.2217/imt.15.69. PMID 26598956.
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