Lebrikizumab met both co-primary and key secondary end points at Week 16 in pediatric patients aged 6 months to 18 years with moderate-to-severe atopic dermatitis, according to a press release from Eli Lilly and Company.
In the Phase 3 ADorable-1 trial, 63% of patients receiving lebrikizumab achieved at least a 75% reduction from baseline in the Eczema Area and Severity Index (EASI), compared with 22% of patients receiving placebo. Additionally, 44% of patients treated with lebrikizumab achieved an Investigator’s Global Assessment (IGA) score of 0 or 1—indicating clear or almost clear skin—with at least a 2-point improvement from baseline, vs 15% with placebo.
Study Design
ADorable-1 was a randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 363 pediatric patients. Participants received either placebo or weight-based lebrikizumab. Topical corticosteroids were initiated 2 weeks before randomization and continued throughout the 16-week treatment period, with the option to taper or discontinue once patients achieved an IGA score of 2 or less.
The co-primary end points were a 75% reduction in EASI score and an IGA score of 0 or 1 at Week 16. Key secondary end points included a 90% reduction in EASI score and a 4-point or greater improvement in Pruritus Numeric Rating Scale score among patients aged 6 years and older with a baseline score of at least 4.
Efficacy Results
At Week 16, 39% of patients receiving lebrikizumab achieved a 90% reduction in EASI score, compared with 11% of patients receiving placebo.
Among eligible patients aged 6 years and older, 35% of those receiving lebrikizumab achieved a clinically meaningful improvement in itch score, defined as a reduction of at least 4 points on the Pruritus Numeric Rating Scale, vs 6% with placebo.
Safety
The safety profile of lebrikizumab was consistent with prior studies in adults and adolescents, with no new safety signals reported. The most common adverse events occurring in at least 5% of participants were upper respiratory tract infections and nasopharyngitis, with similar rates observed between treatment groups. Injection site reactions were also reported at comparable rates, and no injection site pain was reported.
Context and Limitations
Atopic dermatitis (AD) affects approximately 9.6 million children in the United States, with about one-third having moderate-to-severe disease. According to the press release, younger pediatric patients have fewer approved treatment options than adolescents and adults.
ADorable-1 evaluated a 16-week induction period. A long-term extension study, ADorable-2, is ongoing and will follow patients for up to 52 weeks. As these findings are based on topline data, full analyses have not yet been disclosed.
Lebrikizumab is currently approved for the treatment of AD in adults and adolescents aged 12 years and older weighing at least 40 kg. Lilly stated that it plans to submit these data to regulatory agencies for a potential label expansion.
Mechanism
Lebrikizumab is a monoclonal antibody that selectively targets interleukin-13, a cytokine involved in type 2 inflammation associated with AD. By binding to interleukin-13, lebrikizumab inhibits downstream signaling pathways that contribute to skin inflammation and barrier dysfunction.
Investigator Perspective
“Despite the high prevalence of moderate-to-severe [AD] in infants and young children, they have fewer approved treatment options than adults and adolescents,” said Amy Paller, MD, chair of dermatology at Northwestern University and an ADorable study investigator, in the press release. “The topline results from ADorable-1 offer hope for these young patients, delivering near-complete skin clearance and significant itch relief with a highly selective medicine that targets the underlying inflammation that drives this chronic disease.”
Source: Eli Lilly and Company, the manufacturer of lebrikizumab
