20 September 2022 - - The Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending to extend the approval of Adtralza (tralokinumab) in the European Union to include adolescents aged 12 to 17 with moderate-to-severe atopic dermatitis who are candidates for systemic therapy, Danish medical dermatology company Leo Pharma A/S said.

The recommended dose for adolescent patients is an initial dose of 600 mg followed by 300 mg administered every other week, which is the same dosing as for adult patients.

Adtralza, a high-affinity human monoclonal antibody, is approved for the treatment of adults with moderate-to-severe AD in the EU, Great Britain, Canada, the United Arab Emirates, and Switzerland.

It also is approved for adults in the United States under the tradename Adbry. It is not currently approved in any market for adolescent use.

The CHMP opinion is based on data from the Phase 3 ECZTRA 6 trial, which evaluated the efficacy and safety of Adtralza (150 mg or 300 mg) monotherapy compared to placebo in adolescents with moderate-to-severe AD who were candidates for systemic therapy.

Primary endpoints were the Investigator Global Assessment score of clear or almost clear skin (IGA 0/1) and at least a 75% improvement in the Eczema Area and Severity Index score (EASI-75).

Secondary endpoints were measured by extent and severity of atopic dermatitis (SCORAD), at least a 4-point improvement in adolescent weekly average Worst Daily Pruritus Numeric Rating Scale score, and Children's Dermatology Life Quality Index (CDLQI) score.

The CHMP's positive opinion will be reviewed by the European Commission and pending the final decision, the marketing authorization will be valid in all EU Member States, Iceland, Norway, and Liechtenstein.

An additional regulatory filing is underway with the US Food and Drug Administration.

ECZTRA 6 (ECZema TRAlokinumab trial No. 6) is a randomized, double-blind, placebo-controlled, parallel-group, multinational 52-week trial, including a total of 301 patients (aged 12 to 17), with 289 (195 Adtralza patients and 94 placebo patients) in the full analysis set, evaluating the efficacy and safety of Adtralza (150 mg or 300 mg) monotherapy compared to placebo in adolescents with moderate-to-severe atopic dermatitis who were candidates for systemic therapy.

Following a washout period, patients were randomized to subcutaneous Adtralza 150 mg or 300 mg Q2W, or placebo for an initial 16 weeks.

Adtralza dosing started with a 300 mg or 600 mg loading dose on day 0 for those receiving Adtralza 150 mg or 300 mg Q2W, respectively.

At Week 16, patients who responded to Adtralza with an IGA score of 0/1 and/or EASI change of at least 75% from baseline, without use of rescue treatment, were re-randomized to Adtralza Q2W or Q4W for an additional 36 weeks.

Patients not achieving primary endpoints at week 16, those receiving rescue treatment from week 2 to week 16, and those meeting other specific criteria were transferred to open-label treatment of Adtralza 300 mg Q2W plus optional mild-to-moderate strength topical corticosteroids.

Atopic dermatitis is a chronic, inflammatory skin disease characterized by intense itch and eczematous lesions.

Atopic dermatitis is the result of skin barrier dysfunction and immune dysregulation, leading to chronic inflammation.

Type 2 cytokines, including IL-13, play an important role in atopic dermatitis pathophysiology.

Adtralza (tralokinumab) is a high-affinity human monoclonal antibody developed to bind to and inhibit the interleukin -13 cytokine, which plays a role in the immune and inflammatory processes underlying atopic dermatitis signs and symptoms.

Adtralza specifically binds to the IL-13 cytokine, thereby inhibiting interaction with the IL-13 receptor α1 and α2 subunits (IL-13Rα1 and IL-13Rα2).