Dupilumab

From Wikipedia, the free encyclopedia
Dupilumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL4 receptor alpha
Clinical data
Trade namesDupixent
AHFS/Drugs.comMonograph
MedlinePlusa617021
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6512H10066N1730O2052S46
Molar mass146898.98 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 eczema (atopic dermatitis), asthma and nasal polyps which result in chronic sinusitis.[3][4][5][1]

Side effects include decreased levels of T helper cells, cold sores, allergic reactions and inflammation of the cornea.[4] It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme.[6][7] It received approval from the United States Food and Drug Administration (FDA) for moderate-to-severe atopic dermatitis in 2017[4] and for asthma in late 2018.[1] The FDA considers it to be a first-in-class medication.[8]

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).[1][2][9][10]

Side effects[]

Dupilumab can cause allergic reactions, conjunctivitis, and keratitis and, due to its immunosuppressive effects, reactivation of cold sores.[4] In clinical trials, people receiving dupilumab had decreased levels of T helper cells.[11]

There is one reported case of dupilumab triggering hair growth in a patient with complete hair loss.[12] This is being investigated as an unintended, but positive, side effect.

One other case reports a possibility of chronic eosinophilic pneumonia associated with dupilumab.[13]

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.[14]

Pharmacology[]

Mechanism of action[]

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[15] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathways.[11]

Pharmacokinetics[]

Dupilumab shows a non-linear rate in regard to the target.[11] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring one week after injection.[11]

Development[]

Regeneron Pharmaceuticals and Sanofi Genzyme jointly developed Dupilumab,[16] the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies.[17] Phase II trials for asthma treatment showed increased lung function with increased forced expiratory volume for patients.[11]

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.[18] In these trials 38% and 36% of patients respectively, met the primary efficacy goal of the trial, compared to 8% and 10% under placebo.[11]

The United States Food and Drug Administration granted it priority review status[19][20] and in March 2017, the U.S. Food and Drug Administration approved dupilumab injection to treat adults with moderate-to-severe eczema.[4]

References[]

  1. ^ a b c d "Dupixent- dupilumab injection, solution". DailyMed. 25 June 2020. Retrieved 17 September 2020.
  2. ^ a b "Dupixent EPAR". European Medicines Agency (EMA). Retrieved 23 September 2021.
  3. ^ "Statement on a Nonproprietary Name Adopted By The USAN Council - Dupilumab", American Medical Association.
  4. ^ a b c d e "FDA approves new eczema drug Dupixent". FDA. 2019-09-10.
  5. ^ "FDA approves first treatment for chronic rhinosinusitis with nasal polyps". U.S. Food and Drug Administration (FDA). 26 June 2019. Retrieved 27 June 2019.
  6. ^ "Sanofi - Commercial collaboration". Sanofi. Retrieved 2017-03-09.
  7. ^ "A powerful research and development engine". www.regeneron.com. Retrieved 2017-03-09.
  8. ^ New Drug Therapy Approvals 2017 (PDF) (Report). U.S. Food and Drug Administration (FDA). January 2018. Retrieved 16 September 2020.
  9. ^ 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.
  10. ^ 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.
  11. ^ a b c d e f Shirley M (July 2017). "Dupilumab: First Global Approval". Drugs. 77 (10): 1115–1121. doi:10.1007/s40265-017-0768-3. PMID 28547386. S2CID 207489287.
  12. ^ 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. S2CID 52957574.
  13. ^ 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.
  14. ^ 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. 2 (11): 2126–2130. doi:10.1007/s42399-020-00510-x. ISSN 2523-8973. PMC 7483051. PMID 32935079.
  15. ^ 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.
  16. ^ "Sanofi Genzyme Head on Incredible Success of "Once-in-a-Career" Product Dupixent®".
  17. ^ "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Retrieved 2017-10-20.
  18. ^ 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.
  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.
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