Dupilumab, an interleukin-4 receptor alpha antagonist, is a human monoclonal antibody of the IgG4 subclass that binds to the IL-4Rα subunit and inhibits IL-4 and IL-13 signaling. Dupilumab has an approximate molecular weight of 147 kDa.
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PARAMETER |
DATA |
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Manufacturer |
Regeneron Pharmaceuticals, Inc. |
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Indication |
DUPIXENT is an interleukin-4 receptor alpha antagonist indicated for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids. |
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Cell Substrate |
Recombinant human IgG4 monoclonal antibody |
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Manufacturing platform |
The manufacture of dupilumab AS represents a standard manufacturing process for the manufacture of monoclonal antibodies. It is achieved in three main parts, the upstream process, which produces the antibody, the downstream process, which purifies the antibody and the formulation of the active substance (formulated active substance- FAS). Dupilumab is produced by a cell culture process with recombinant Chinese hamster ovary (CHO) cells that have been engineered to constitutively express dupilumab heavy and light chains. Dupilumab protein is expressed by the cells and is secreted into the culture medium. The recombinant protein product is harvested and purified leveraging standard chromatographic and membrane based techniques and includes several steps ensuring adventitious agent safety. At the conclusion of purification, the AS is sterile-filtered and dispensed for long-term storage until needed for formulation. |
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Dose in vial/final container |
300 mg/2 mL solution in a single-dose pre-filled syringe |
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Dose to patient |
600 mg (two 300 mg injections in different injection sites), followed by 300 mg given every other week. |
CLINICAL TRIALS
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NCT |
TRIAL PHASE |
NO OF PATIENTS ENROLLED |
STUDY TITLE |
COUNTRIES |
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Controlled Studies to Support Efficacy and Safety |
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NCT02277743 |
3 |
671 |
United States, Bulgaria, Canada, Denmark, Estonia, Japan, Spain, Finland, Germany, Singapore |
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NCT02277769 |
3 |
708 |
United States, Canada, Italy, France, Germany, Hong Kong, Korea, Republic of, Lithuania, Poland, Sweden, United Kingdom |
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NCT02260986 |
3 |
740 |
United States, Canada, Italy, Australia, Czechia, Hungary, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, Romania, United Kingdom |
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Dose-Ranging Study; Supports Safety |
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NCT01859988 |
2 |
380 |
Study of Dupilumab Administered to Adult Patients with Moderate-to-Severe Atopic Dermatitis |
United States, Canada, Czechia, Germany, Japan, Hungary, Poland |
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PD and PK PD Studies; Support Safety |
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NCT01979016 |
2 |
54 |
Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD) |
United States, Canada |
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NCT02210780 |
2 |
194 |
Study of Dupilumab and Immune Responses in Adults with Atopic Dermatitis (AD) |
United States |
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NCT01548404 |
2 |
109 |
Study of Dupilumab in Adult Patients with Extrinsic Moderate-to-Severe Atopic Dermatitis |
Czechia, France, Germany, Hungary, Poland |
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Uncontrolled Clinical Study |
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NCT01949311 |
3 |
2678 |
Open-label Study of Dupilumab in Patients with Atopic Dermatitis |
United States, Austria, Italy, Australia, Belgium, France, Bulgaria, Canada, China, Czechia, Japan, Denmark, Estonia, Finland, Germany, Hungary, Ireland, Lithuania, Korea, Republic of, New Zealand, Poland, Spain, Slovakia, Romania, Russian Federation, Singapore, Netherlands, United Kingdom |
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US Approval |
March 28, 2017 |
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EU Approval |
September 27, 2017 |
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Health Canada Approval |
September 27, 2019 |
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Japanese Ministry of Health, Labor and Welfare (MHLW) Approval |
January 22, 2018 |
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TGA |
January 22, 2018 |
No advisory committee meeting was held for this application. Although dupilumab is a new molecular entity and first-in class, the application itself did not present novel issues, not previously discussed, which merited advisory committee input. A related topic, the timing of pediatric development of systemic products for treatment of patients with moderate to severe atopic dermatitis not adequately controlled with optimized topical therapy, was presented to the Dermatology and Ophthalmology Drug Advisory Committee (DODAC) on 9 March 2015. At that meeting, preliminary safety, and efficacy data for dupilumab, gleaned from published literature, was presented to DODAC as an example of a relevant product under development. The committee was not asked to comment on the efficacy and safety of dupilumab per se, but rather to address issues related to pediatric development of products for the specified indication.