Dupilumab
[CAS# 1190264-60-8]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism >> PPAR antagonist
• Name: Dupilumab
• Synonyms: Dupixent
• Molecular Weight: 150000
• CAS Registry Number: 1190264-60-8

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

Dupilumab is a fully human monoclonal antibody developed through recombinant DNA technology to target and inhibit the signaling of interleukin-4 (IL-4) and interleukin-13 (IL-13), two key cytokines in the pathophysiology of type 2 (Th2) inflammation. This biologic agent was discovered and co-developed by Regeneron Pharmaceuticals and Sanofi as part of a collaborative effort to address diseases driven by Th2-mediated immune responses. Its mechanism of action and therapeutic potential have led to its approval for multiple indications, including atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

The development of dupilumab originated from the need to find targeted therapies for conditions in which conventional treatments, such as corticosteroids or immunosuppressants, were either inadequate or associated with significant side effects. Using Regeneron’s VelocImmune® platform, a genetically engineered mouse model capable of producing fully human antibodies, scientists identified and optimized an antibody that binds to the shared alpha subunit of the IL-4 and IL-13 receptors. This blockade prevents the signaling of both cytokines, effectively dampening downstream inflammatory pathways involved in allergy, skin inflammation, airway hyperresponsiveness, and mucus overproduction.

Dupilumab was first approved by the U.S. Food and Drug Administration (FDA) in March 2017 for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies. This indication was expanded in subsequent years to include adolescents and children as young as six months old. Clinical trials demonstrated significant improvement in the Eczema Area and Severity Index (EASI) scores, reduction in itching, and enhancement in quality of life measures compared to placebo.

Following its success in dermatology, dupilumab was also investigated for respiratory and ENT indications. It received FDA approval in 2018 as an add-on maintenance therapy for patients with moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. The drug showed a notable reduction in asthma exacerbations, improved lung function (as measured by FEV₁), and allowed for corticosteroid tapering in steroid-dependent patients. This was particularly important in reducing long-term complications associated with systemic steroid use.

In June 2019, dupilumab was approved for the treatment of adults with chronic rhinosinusitis with nasal polyposis (CRSwNP), again showing substantial reductions in polyp size, nasal congestion, and need for surgical intervention. It became the first biologic approved for this condition, offering a new option for patients who had previously required repeated endoscopic sinus surgeries.

Beyond its approved indications, dupilumab continues to be evaluated for a range of other Th2-driven diseases. These include eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and food allergies. Results from ongoing clinical trials suggest its broader utility in modulating allergic and eosinophilic pathways across organ systems.

The administration of dupilumab is by subcutaneous injection, typically every two or four weeks depending on the indication and patient weight. It is generally well tolerated; the most common side effects include injection site reactions, conjunctivitis, and nasopharyngitis. Importantly, its targeted mechanism does not result in general immunosuppression, making it safer for long-term use compared to traditional systemic therapies.

Dupilumab represents a landmark in the advancement of precision medicine in immunology, offering a biologic option that addresses the underlying cytokine drivers of disease rather than merely managing symptoms. Its discovery and development have helped shift the treatment paradigm in chronic allergic and inflammatory disorders by introducing cytokine-targeted therapy with high efficacy and an acceptable safety profile.

References

2013. Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. The New England Journal of Medicine, 368(26).
DOI: 10.1056/NEJMoa1304048

2016. Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA, 315(5).
DOI: 10.1001/jama.2015.19330