Regulatory Decision Summary for Adtralza

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, relapsing, inflammation of the skin that is characterized by intractable pruritus, extensive xerosis (abnormally dry and scaly skin), and skin lesions. The clinical manifestations of AD can lead to psychological and sociological sequelae that have a negative impact on patients’ lives. The main goal of the treatment of AD is the reduction of inflammation and symptoms, in particular, pruritus. However, the management of moderate-to-severe AD has been challenging because of the chronicity of the disease and the limited therapeutic options that are both efficacious and have a tolerable long-term safety profile.

The benefits of Adtralza in the treatment of moderate-to-severe atopic dermatitis (AD) are primarily based on clinical data from three randomized, double-blind, placebo-controlled trials, ECZTRA 1 (monotherapy), ECZTRA 2 (monotherapy), and ECZTRA 3 (combination with topical corticosteroids [TCS]), that enrolled a total of 1,976 patients 18 years of age and older. All three pivotal trials assessed the superiority of Adtralza compared to placebo through the co-primary endpoints at Week 16, the change from baseline in the proportion of patients with an Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) and the proportion of patients with Eczema Area and Severity Index-75 (EASI-75) (an improvement of at least 75% in EASI score from baseline). At Week 16, Adtralza was shown to be statistically significant and relatively modestly clinically meaningful in terms of IGA 0/1 and EASI-75 responses compared to placebo both as a monotherapy or in combination with TCS; maintenance of efficacy was also observed up to 52 weeks. Secondary endpoints measuring specific symptoms (i.e., pruritus), anxiety and depression, sleep disturbances, and quality of life were all supportive of a favourable benefit associated with Adtralza as measured by the co-primary endpoints.

The safety profile of Adtralza in adults with moderate-to-severe AD was evaluated in 1,991 subjects, including 807 subjects exposed for at least 52 weeks across the three pivotal phase 3 studies, is considered acceptable. The safety profiles of Adtralza were consistent between monotherapy studies and the combination therapy study (with concomitant TCS). There was an increased incidence of eye disorders (conjunctivitis and keratitis), as well as eosinophilia in Adtralza-treated subjects; however, cases were of mild to moderate severity and resulted in few patients discontinuing the study drug. Adtralza was generally well-tolerated.

The recommended dose of the drug is an initial 600 mg dose followed by 300 mg every 2 weeks. In certain patients who demonstrate an efficacious response after 16 weeks, dosing of 300 mg every 4 weeks may be considered. View the Product Monograph for details.

Overall, based on the data evaluated as part of this submission, the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) considers there to be sufficient evidence at this time to conclude that the benefit-risk profile for Adtralza (tralokinumab injection) for the treatment of moderate-to-severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable is considered favourable.