Phase 3 Studies Show Lebrikizumab Effective in Patients With Moderate-to-Severe Atopic Dermatitis

After 16 weeks of treatment, lebrikizumab (Almirall) was effective in adolescents and adults with moderate-to-severe atopic dermatitis, according to two Phase 3 studies. The research was published in the New England Journal of Medicine.  

Lebrikizumab is a novel, investigational, monoclonal antibody designed to bind IL-13 with high affinity, slow disassociation rate and high potency to specifically prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signalling, thereby inhibiting the biological effects of IL-13 in a targeted and efficient fashion. AD is an IL-13 dominant disease in which IL-13 drives skin barrier dysfunction, itch, skin thickening, and susceptibility to infection.

Researchers conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, Phase 3 trials. Both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2), or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks.

The primary outcome was an Investigator’s Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.

In trial 1, the primary outcome was met in 43.1% of 283 patients in the lebrikizumab group, and in 12.7% of 141 patients in the placebo group (P<0.001); an EASI-75 response occurred in 58.8% and 16.2%, respectively (P<0.001).

In trial 2, the primary outcome was met in 33.2% of 281 patients in the lebrikizumab group, and in 10.8% of 146 patients in the placebo group (P<0.001); an EASI-75 response occurred in 52.1% and 18.1%, respectively (P<0.001).

Measures of itch and itch interference with sleep indicated improvement with lebrikizumab therapy. The incidence of conjunctivitis was higher among patients who received lebrikizumab than among those who received placebo. Most adverse events during the induction period were mild or moderate in severity and did not lead to trial discontinuation.

The study authors concluded that in the induction period of two phase 3 trials, 16 weeks of treatment with lebrikizumab was effective in adolescents and adults with moderate-to-severe atopic dermatitis.

In October, the European Medicines Agency (EMA) accepted the filing of the Marketing Authorization Application (MAA) for lebrikizumab for the treatment of moderate to severe atopic dermatitis. The MAA filing is based on three pivotal Phase 3 studies: ADvocate 1 and ADvocate 2, evaluating lebrikizumab as monotherapy in adult and adolescent patients with moderate-to-severe AD; and ADhere, assessing lebrikizumab in combination with topical corticosteroids (TCS).

Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe. Eli Lilly and Company has exclusive rights for the development and commercialization of lebrikizumab in the United States and the rest of the world, not including Europe.