Dupilumab


Dupilumab, sold under the trade name Dupixent, is a monoclonal antibody used for allergic diseases such as eczema, asthma and nasal polyps which result in chronic sinusitis.
Side effects include allergic reactions, cold sores, and inflammation of the cornea. It was developed by Regeneron Pharmaceuticals and Sanofi Genzyme. It received approval from the United States Food and Drug Administration for moderate-to-severe atopic dermatitis in 2017 and for asthma in late 2018. As of 2019 it costs about 46,000 per year.

Medical uses

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

Side effects

Dupilumab can cause several side effects including allergic reactions, conjunctivitis, and keratitis.
There is one reported case of dupilumab triggering hair growth in a patient with complete hair loss. 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, making it a receptor antagonist. 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.

Pharmacokinetics

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

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.
The United States Food and Drug Administration granted it priority review status. On March 28, 2017, the U.S. Food and Drug Administration approved dupilumab injection to treat adults with moderate-to-severe eczema.
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.
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.
Phase II trials for asthma treatment showed increased lung function for patients, showing increased forced expiratory volume.