Development

Eli Lilly's lebrikizumab delivers positive Phase 3 results in pediatric atopic dermatitis trial

Eli Lilly announced positive Phase 3 results for EBGLYSS (lebrikizumab-lbkz) in pediatric patients aged six months to 18 years with moderate-to-severe atopic dermatitis. The ADorable-1 trial met both co-primary endpoints at Week 16, generating the first Phase 3 dataset for a selective IL-13 inhibitor in children as young as six months, a population with limited approved systemic treatment options.

Trial specifics

ADorable-1 (NCT05559359) is a randomized, double-blind, placebo-controlled Phase 3 study that enrolled 363 pediatric participants with moderate-to-severe atopic dermatitis. Patients were randomized to receive placebo or weight-based doses of lebrikizumab. All participants used topical corticosteroids beginning two weeks before randomization and throughout the 16-week treatment period, though tapering was permitted once patients reached an Investigator's Global Assessment score of 2 or less.

At Week 16, 63% of lebrikizumab-treated patients achieved EASI-75, compared with 22% on placebo. For the second co-primary endpoint, 44% of lebrikizumab-treated patients achieved IGA 0 or 1 with a reduction of at least 2 points from baseline, versus 15% on placebo. Among key secondary endpoints, 39% of patients on lebrikizumab reached EASI-90 compared with 11% on placebo, and 35% of patients aged six years and older achieved a Pruritus NRS improvement of at least 4 points, versus 6% on placebo. The company did not disclose p-values or confidence intervals in its topline announcement.

The safety profile was consistent with that observed in adult and adolescent studies, the company said, with no new signals identified. Upper respiratory tract infections and nasopharyngitis were the most common adverse events occurring in 5% or more of participants, with no numerical imbalance between arms. No injection site pain was reported in either group.

Lilly stated it plans to submit these data to the US FDA and other global regulators to support a potential label expansion into younger pediatric populations. The ADorable program continues, with results from ADorable-2, a 52-week extension study of ADorable-1 participants, expected later this year. EBGLYSS received US FDA approval in 2024 for adults and children aged 12 years and older weighing at least 40 kg with moderate-to-severe atopic dermatitis not adequately controlled by topical prescription therapies. The drug was approved in the EU in 2023 and in Japan and Canada in 2024.

The AllSci BriefSystematic R&D and deal news. Daily.

Research context

Lebrikizumab is a monoclonal antibody that binds soluble IL-13 at a site overlapping with the IL-4Rα binding region on the IL-13Rα1/IL-4Rα receptor complex, preventing receptor assembly and downstream signaling. IL-13 is considered a central driver of type 2 inflammation in atopic dermatitis, contributing to skin barrier dysfunction, epidermal thickening, pruritus, and susceptibility to infection. By selectively neutralizing IL-13 without blocking IL-4, lebrikizumab differs mechanistically from dupilumab, which targets the shared IL-4Rα subunit used by both cytokines.

Atopic dermatitis affects an estimated 9.6 million children in the United States, according to the company, with roughly one-third experiencing moderate-to-severe disease. Treatment options for younger children remain more limited than those available to adults and adolescents. Topical corticosteroids and calcineurin inhibitors remain first-line therapy, while systemic options have expanded in recent years for older patients. The ADorable-1 data, if they support regulatory approval, could extend the labeled use of lebrikizumab to patients as young as six months.

Key competitors include:

  • Sanofi and Regeneron's dupilumab, an IL-4Rα antagonist that received US FDA approval for children aged six months to five years with moderate-to-severe atopic dermatitis in 2022, making it the first biologic approved for this age group.
  • LEO Pharma's tralokinumab, another IL-13 inhibitor approved for adults, with ongoing Phase 3 pediatric studies.
  • AbbVie's upadacitinib, an oral JAK1 inhibitor approved for adults and adolescents with moderate-to-severe atopic dermatitis, with pediatric studies underway.

Spot something wrong? Report an issue with this article