Dupilumab

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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

Dupilumab, sold under the trade name Dupixent, is a monoclonal antibody designed for the treatment of allergic diseases such as eczema (atopic dermatitis).[1][2] Side effects include allergic reactions, cold sores, and inflammation of the cornea.[2] It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme.[3][4] It received FDA approval for moderate-to-severe atopic dermatitis in 2017.[2] As of 2017 it costs about 37,000 USD per year.[5]

Medical uses[edit]

It appears to be useful for moderate-to-severe atopic dermatitis for which it is approved in the United States.[6][7] It is also being evaluated for treatment of persistent asthma in adults and adolescents.[7][8]

Side effects[edit]

Dupilumab has the ability to 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.[9] This is being investigated as an unintended, but positive side effect.

Pharmacology[edit]

Mechanism of action[edit]

Dupilumab binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[10] 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.[11]

Pharmacokinetics[edit]

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 1 week post injection.[11]

Development[edit]

Development of dupilumab was a joint effort by Regeneron and Sanofi, the latter of which provided 130 million dollars to Regeneron for research and development towards monoclonal antibodies.[12]

The US FDA granted it priority review status.[13][14] On March 28, 2017, the U.S. Food and Drug Administration approved dupilumab injection to treat adults with moderate-to-severe eczema.[2]

As per the FDA, dupilumab was manufactured in accordance with current GMP.[15] In October 2016, Regeneron posted a phase III CHRONOS trial, contrasting dupilumab with topical corticosteroids. The study showed that in conjunction with topical corticosteroids, people had a larger decrease in symptoms than steroids alone.[16]

Phase III SOLO 1 and SOLO 2 trials were also performed, which evaluated 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.[11]

Phase II trials for asthma treatment showed increased lung function for patients, showing increased levels of forced expiratory volume.[11]

References[edit]

  1. ^ Statement On A Nonproprietary Name Adopted By The USAN Council - Dupilumab, American Medical Association.[dead link]
  2. ^ a b c d e "FDA approves new eczema drug Dupixent". FDA.
  3. ^ "Sanofi - Commercial collaboration". Sanofi. Retrieved 2017-03-09.
  4. ^ "Pipeline | A powerful research and development engine". www.regeneron.com. Retrieved 2017-03-09.
  5. ^ 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.
  6. ^ 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.
  7. ^ a b 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.
  8. ^ Castro, Mario; Corren, Jonathan; Pavord, Ian D.; Maspero, Jorge; Wenzel, Sally; Rabe, Klaus F.; Busse, William W.; Ford, Linda; Sher, Lawrence (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.
  9. ^ 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. doi:10.1001/jamadermatol.2018.2976. PMID 30304403.
  10. ^ [ Dupilumab in Persistent Asthma with Elevated Eosinophil Levels - Sally Wenzel, M.D., Linda Ford, M.D., David Pearlman, M.D., Sheldon Spector, M.D., Lawrence Sher, M.D., Franck Skobieranda, M.D., Lin Wang, Ph.D., Stephane Kirkesseli, M.D., Ross Rocklin, M.D., Brian Bock, D.O., Jennifer Hamilton, Ph.D., Jeffrey E. Ming, M.D., Ph.D., Allen Radin, M.D., Neil Stahl, Ph.D., George D. Yancopoulos, M.D., Ph.D., Neil Graham, M.D., and Gianluca Pirozzi, M.D., Ph.D.], NEJM.
  11. ^ a b c d e Shirley, Matt (2017-07-01). "Dupilumab: First Global Approval". Drugs. 77 (10): 1115–1121. doi:10.1007/s40265-017-0768-3. ISSN 0012-6667.
  12. ^ "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Retrieved 2017-10-20.
  13. ^ "Novel Biologic Dupilumab Improves Eczema Symptoms". Retrieved 30 October 2017.
  14. ^ Walker, Joseph (2016-05-30). "New Eczema Treatments Could Be Available Soon". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-05-31.
  15. ^ "FDA Active Division Director Summary Review" (PDF). FDA. Retrieved 2017-10-25.
  16. ^ Hamilton, Jennifer D.; Ungar, Benjamin; Guttman-Yassky, Emma (2015). "Drug evaluation review: dupilumab in atopic dermatitisjournal=Immunotherapy". Immunotherapy. 7 (10): 1043–1058. doi:10.2217/imt.15.69. PMID 26598956.