Dupilumab, a monoclonal antibody that targets both interleukin-4 and interleukin-13, has been approved for the treatment of moderate to severe atopic dermatitis in adults not adequately controlled with topical prescription therapies or for whom topicals are not appropriate.
The approval marks the first biologic approved for treating AD, according to a March 28 announcement from the Food and Drug Administration.
Dupilumab “inhibits signaling of IL-4 and IL-13, two key cytokines required for the type 2 (including Th2) immune response, which is believed to be a major driver in the pathogenesis of the disease,” according to Regeneron, which will market dupilumab.
Approval was based on three phase III pivotal studies of adults with moderate to severe AD whose disease was not adequately controlled with topical prescription treatments: SOLO-1 and SOLO-2, which evaluated dupilumab as monotherapy, and the CHRONOS study, which compared dupilumab with topical corticosteroids to treatment with topical corticosteroids alone.
The 16-week data from the SOLO-1 and -2 studies were presented at the 2016 annual congress of the European Academy for Dermatology and Venereology.
In two phase III trials of identical design involving patients with atopic dermatitis, dupilumab, administered weekly or every 2 weeks, improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P less than .001 for all comparisons).
Dupilumab also was associated with improvement in other clinical endpoints, including reductions in pruritus and symptoms of anxiety or depression, and an improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. The results were published in the New England Journal of Medicine (2016;375:2335-48).
More recently, 52-week data from the CHRONOS study were reported at the annual meeting of the American Academy of Dermatology in March. In that study of 740 adults with moderate to severe AD that was not controlled with topical medications – including corticosteroids with or without calcineurin inhibitors – those randomized to 300 mg of dupilumab once a week, plus topical corticosteroids, showed significantly greater improvements in measures of overall disease severity at 16 weeks and at 52 weeks, compared with those treated with steroids alone. Measures used included Eczema Area and Severity Index and the Pruritus Numerical Rating Scale, Patient Oriented Eczema Measure, Dermatology Life Quality Index.
Adverse events experienced with dupilumab included injection site reactions, eye and eyelid inflammation, and cold sores on the mouth or lips, according to a Regeneron statement.
Dupilumab will be available “later this week,” according to the statement, which noted the wholesale acquisition cost of the medication is expected to be $37,000 annually.
The FDA approval announcement noted that the safety and efficacy of dupilumab had not been established in patients with asthma.
Dupilumab currently is being studied for children with AD in phase II studies and is being studied for other indications: eosinophilic esophagitis in phase II studies, and asthma and nasal polyps in phase III studies.
Dupilumab will be marketed as Dupixent by Regeneron.