67 | LEBRIKIZUMAB FOR PAEDIATRIC PATIENTS AGED ≥6 MONTHS WITH MODERATE-TO-SEVERE AD: PHASE 3 ADORABLE-1 WEEK-16 RESULTS

L. Stingeni¹, L. Eichenfield², J. Ornelas³, V. Prajapati⁴, C. Yang⁵, A. Tanaka⁶, S. Weidinger⁷, C. Flohr⁸, E. Swanson⁹, L. Martin¹⁰, S. Daveiga¹¹, R. Gontijo Lima¹¹, H. Elmaraghy¹¹, E. Pierce¹¹, P. Sen¹¹, G. Gallo¹¹, M. Piruzeli¹¹, A. Larkin¹¹, M. Grau¹², Y. Mihaylov¹², A. Paller¹³ | ¹Dermatology Section, Department of Medicine and Surgery, University of Perugia, Italy; ²Departments of Dermatology and Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA; ³Department of Dermatology, Integrative Skin Science and Research, Sacramento, California, USA; ⁴Dermatology Research Institute, Skin Health & Wellness Centre, Probity Medical Research, and University of Calgary, Calgary, Canada; ⁵Chang Gung University College of Medicine, Taoyuan, Taiwan; ⁶Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; ⁷Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Lübeck, Germany; ⁸Department of Dermatology and Population Health Sciences, King’s College London, UK; ⁹Ada West Dermatology, St Luke’s Children’s Hospital Idaho, USA; ¹⁰School of Clinical Medicine, UNSW Sydney & Dermatology Department, Sydney Children’s Hospital, Sydney, Australia; ¹¹Eli Lilly and Company, Indianapolis, Indiana, USA; ¹²Almirall R&D, S.A., Barcelona, Spain; ¹³Dermatology and Infectious Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

Background and Objectives. To evaluate the efficacy and safety of lebrikizumab compared to placebo (PBO) in patients 6 months to <18 years of age with moderate-to-severe atopic dermatitis (AD) in the randomised, double-blind, PBO-controlled, Phase 3 ADorable-1 study (NCT05559359). AD is the most prevalent systemic chronic inflammatory skin condition in children, affecting 15–20% worldwide1. There is a significant unmet need due to limited treatment options: only one biologic option is approved for use in patients as young as 6 months of age with moderate-to-severe AD. Lebrikizumab binds interleukin-13 with high binding affinity and slow dissociation rate. Interleukin-13 is a key driver of AD pathogenesis. Lebrikizumab is currently approved for adolescent patients aged ≥12 years, weighing ≥40 kg with moderate-to-severe AD.
Methods. Key inclusion criteria. Age ≥6 months to <18 years. Weight minimum ≥6 kg for all patients, and <40 kg for patients aged ≥12 to <18 years. EASI score ≥16. IGA score ≥3 (on a 0–4 scale). ≥10% body surface area (BSA) involvement. Diagnosis of AD per American Academy of Dermatology criteria, with duration requirements tiered by age: – ≥12 months if the participant was ≥6 years old – ≥6 months if 2 to <6 years old – ≥3 months if 6 months to <2 years old Key exclusion criteria. Prior treatments before baseline: – Dupilumab within 8 weeks (enrollment of patients with prior dupilumab use was capped at <20% of the study population) – Other biologics within 5 half-lives (if known) or 16 weeks, whichever is longer TCS standardisation. Two weeks before the baseline visit, a standardised topical corticosteroid (TCS) treatment was initiated for all patients and continued through the end of the study. TCS use was tapered upon lesion clearance (IGA ≤2 → 3×/week; IGA 0 → stop), alongside daily non-medicated emollient use throughout the study Rescue medication. Rescue medication included high or ultra-high-potency TCS, and any systemic AD treatment Analysis populations. Efficacy analyses used the overall Intent-to-Treat (ITT) population. Safety analyses used the Overall Safety population Statistical analyses. Treatment comparisons used the Cochran‑Mantel‑Haenszel test stratified by geographic region, age group at first visit and disease severity. Primary method of handling missing efficacy data (non-responder imputation/multiple imputation [NRI/MI]): – Patients who received rescue medication were analysed as non-responders – For patients who discontinued treatment for any reason, observed data after treatment discontinuation were used; Markov chain Monte Carlo multiple imputation was used to handle the remaining missing data. The family-wise type 1 error is controlled at a 2-sided level of 0.05 using the graphical multiple testing strategy. The overall ITT population is defined as all randomised patients from Cohort 1 and all randomised patients from Cohort 2 who either complete or have an opportunity to complete treatment through Week 16 at the time of the data cut. The Overall Safety population is defined as all randomised patients from Cohorts 1 and 2 who received ≥1 dose of study treatment and who either complete or have an opportunity to complete treatment through Week 16.
Conclusions. In the Phase 3 ADorable‑1 study, lebrikizumab demonstrated statistically significant and clinically meaningful efficacy versus PBO, meeting both co‑primary endpoints of Investigator’s Global Assessment (IGA) 0/1 with ≥2-point improvement and Eczema Area And Severity Index (EASI) 75 at Week 16 in patients aged 6 months to <18 years with moderate‑to‑severe AD. Treatment with lebrikizumab resulted in consistent improvements in key measures of disease severity and symptoms (skin clearance, itch relief and quality of life). The safety profile of lebrikizumab in ADorable-1 was consistent with prior studies in adult and adolescent patients with moderate-to-severe AD, and no new safety findings were identified over 16 weeks of treatment. These results provide evidence supporting interleukin-13-targeted therapy as a novel treatment for a broad paediatric population.