Dupilumab

    Dupilumab is a fully human investigational monoclonal antibody delivered by subcutaneous injection that targets the alpha subunit of the interleukin 4 receptor (IL-4R alpha). By blocking IL-4R alpha, dupilumab modulates signaling of both IL-4 and IL-13, drivers of Th2 (Type 2 helper T cell) immune response. Dupilumab was created using Regeneron’s VelocImmune® gene modification technologies and is being co-developed with Sanofi. Dupilumab is currently in Phase 2b studies in atopic dermatitis, asthma and nasal polyposis.

    [td_text_with_title custom_title=”Latest post”]

    Pembrolizumab for the treatment of advanced gastric cancer.

    Yung-Jue Bang, MD, PhD, Professor of Medical Oncology, Seoul National University College of Medicine; President, Biomedical Research Institute, Seoul National University Hospital discusses pembrolizumab for the treatment of advanced gastric cancer.

    0 comments
    [/td_text_with_title][td_text_with_title custom_title=”From Wikipedia”]
    Dupilumab
    Monoclonal antibody
    Type Whole antibody
    Source Human
    Target IL4 receptor alpha
    Clinical data
    Trade names Dupixent
    Routes of
    administration
    Injection
    ATC code
    Legal status
    Legal status
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    Chemical and physical data
    Formula C6512H10066N1730O2052S46
    Molar mass 146.9 kg/mol

    Dupilumab, sold under the trade name Dupixent, is a monoclonal antibody designed for the treatment of allergic diseases such as eczema.[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 in 2017.[2] As of 2017 it costs about 37,000 USD per year.[5]

    Medical uses

    It appears to be useful for moderate to severe atopic dermatitis for which it is approved in the United States.[6][7] There is also some evidence of benefit in asthma.[7]

    Side effects

    Dupilumab has the ability to cause several side effects including: allergic reactions, conjunctivitis, and keratitis.[2]

    Pharmacology

    Mechanism of action

    It binds to the alpha subunit of the interleukin-4 receptor (IL-4Rα), making it a receptor antagonist.[8] Through blockade of IL-4Rα, dupilumab modulates signaling of both the interleukin 4 and interleukin 13 pathway. In clinical trials, patients saw decreased levels of Th2 bio-markers.[9]

    Pharmacokinetics

    Dupilumab shows a non-linear rate in regard to the target.[9] Dupilumab is also reported to have a bioavailability of 64%, with the average concentration occurring 1 week post injection.[9]

    Development

    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.[10]

    The US FDA granted it priority review status.[11][12] 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.[13] 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.[14]

    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.[9]

    Phase II trials for asthma treatment showed increased lung function for patients, showing increased levels of forced expiratory volume.[9]

    References

    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. doi:10.1097/MCP.0000000000000438. PMID 29059087. 
    8. ^ [ 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.
    9. ^ 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. 
    10. ^ "SEC 10-Q Filing of Regeneron". SEC.gov. 2017-06-30. Retrieved 2017-10-20. 
    11. ^ "Novel Biologic Dupilumab Improves Eczema Symptoms". Retrieved 30 October 2017. 
    12. ^ Walker, Joseph (2016-05-30). "New Eczema Treatments Could Be Available Soon". Wall Street Journal. ISSN 0099-9660. Retrieved 2016-05-31. 
    13. ^ "FDA Active Division Director Summary Review" (PDF). FDA. Retrieved 2017-10-25. 
    14. ^ Hamilton, Jennifer D.; Ungar, Benjamin; Guttman-Yassky, Emma (2015). "Drug evaluation review: dupilumab in atopic dermatitisjournal=Immunotherapy". 7 (10): 1043–1058. doi:10.2217/imt.15.69. ISSN 1750-7448. PMID 26598956. 
    source: https://en.wikipedia.org/wiki/Dupilumab[/td_text_with_title]