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, that affects adolescent as well as adult patients. The pathophysiology of AD in adolescents is similar to that in adults, and involves genetic, environmental, and immunologic factors that trigger hypersensitivity reactions. The clinical manifestations of AD can lead to psychological and sociological sequelae that have a negative impact on patients’ lives.

Authorization of Adtralza (tralokinumab injection) for use in adolescent patients with moderate-to-severe AD was based on a single international, multi-centre, randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of two dosage regimens of Adtralza in adolescents 12 years and older with moderate-to-severe AD (i.e., 150 mg once every 2 weeks [Q2W] and 300 mg Q2W).

Compared to placebo, both dosage regimens of Adtralza resulted in a clinically and statistically significant differences in the primary endpoints at Week 16, including the proportion of patients achieving Investigator’s Global Assessment (IGA) 0 (clear) or 1 (almost clear) and the proportion of patients achieving EASI75 (an improvement of at least 75% in Eczema Area and Severity Index (EASI) score from baseline). Maintenance of efficacy was also observed up to 52 weeks. Secondary endpoints measuring specific symptoms (i.e., pruritus), anxiety and depression, and quality of life were all supportive of a favourable benefit associated with Adtralza and numerically favoured the Adtralza 300 mg Q2W dosage regimen compared to Adtralza 150 mg Q2W.

The risks associated with Adtralza in adolescents with moderate-to-severe AD were consistent with those in adults. No new adverse reactions or new safety signals were observed. The safety profiles of Adtralza 150 mg Q2W and 300 mg Q2W arms were similar except for a lower incidence of certain skin-related adverse events with Adtralza 300 mg Q2W. Adtralza was generally well-tolerated.

The recommended dose of the drug in adolescents is an initial dose of 600 mg (four 150 mg injections) followed by 300 mg (two 150 mg injections) administered every other week (Q2W) as subcutaneous injection.

The addition of information in the Product Monograph based on a dedicated drug-drug interaction study showing no major interactions, was also deemed acceptable. 

Overall, based on the data evaluated as part of this submission, the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) considers that the benefit-risk profile for Adtralza (tralokinumab injection) is favourable for the treatment of moderate-to-severe atopic dermatitis in adolescent patients 12 years of age and older, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.