New Phase 3b Findings Suggest Lebrikizumab Improved Skin, Itch for Atopic Dermatitis

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Lebrikizumab-lbkz (Ebyglyss) treatment of moderate-to-severe atopic dermatitis leads to improvements in patients’ skin (including hands and face) and itch among those who were previously treated with dupilumab, new findings announced by Elil Lilly and Company suggest.^1,2

These data from the phase 3b ADapt study were presented at the 2024 Fall Clinical Dermatology Conference in Las Vegas. Lebrikizumab is an interleukin (IL)-13 inhibitor which is designed to selectively block IL-13 signaling with high binding affinity. The medication recently was approved by the US Food and Drug Administration (FDA) as a first-line biologic therapy for those aged 12 years and older with moderate-to-severe atopic dermatitis who also weigh at least 88 pounds.

“Treatment isn't one-size-fits-all, and many patients with moderate-to-severe atopic dermatitis remain in need of an effective medicine to help manage the impact of the disease, especially in difficult-to-treat areas like face and hands,” Linda Stein Gold, MD, ADapt study investigator and director of dermatology research for Henry Ford Health System, said in a statement.¹

The cytokine IL-13 is a key element driving atopic dermatitis, specifically involved in the type-2 inflammatory cycle in patients’ skin. This cycle often results in skin barrier dysfunction, skin thickening, pruritus, and infection.

Throughout the ADapt study, Stein Gold and colleagues evaluated the level of safety of efficacy of lebrikizumab for individuals with moderate-to-severe atopic dermatitis who had been treated with dupilumab previously. Those deemed eligible for the analysis had discontinued dupilumab due to such reasons as insufficient treatment response, adverse events, side effects, or other factors such as cost.

During ADapt, the primary endpoint determined by the investigators was a 75% Eczema Area and Severity Index score improvement (EASI-75) at the 16-week mark, during which they would assess the reach and intensity of subjects’ skin condition. In terms of secondary outcomes, the team searched for Investigator Global Assessment (IGA) score of clear (0) or nearly clear (1) skin at the 16 and 24-week mark, with a reduction of at least 2 points from baseline.

In addition, Stein Gold et al. looked at improvements seen among patients in terms of pruritus scores and other exploratory endpoints. In the latest findings from ADapt, the team found that 57% of participants treated with lebrikizumab successfully reached EASI-75 at the 16-week mark, and 60% by the 24-week mark.

These data aligned closely with those of the phase 3 ADvocate 1 and ADvocate 2 studies assessing individuals who had not used dupilumab previously. The investigators also noted that 46% of subjects with an inadequate response to dupilumab who switched achieved EASI-75 with lebrikizumab at the 16-week mark.

The research team further highlighted that 53% of participants who transitioned from dupilumab to lebrikizumab had a 4-point or greater reduction on the Pruritus NRS scale at the 16-week mark, rising to 62% by 24 weeks. In particularly challenging regions, the team also noted improvements, with 52% of subjects achieving clear or almost clear skin on their face by the 24-week mark.

The investigators reported that modified total lesion symptom scores (mTLSS) showed a 75% reduction by the 24-week mark for subjects with severe hand dermatitis. In terms of the medication’s safety profile, it was noted that fewer than 6% of ADapt participants stopped using the drug due to adverse effects.

Lebrikizumab was shown to have a similar safety profile to that of previous phase 3 studies, with no new safety risks observed. The research team highlighted that most side effects were mild to moderate, with common examples including conjunctivitis and reactions at injection sites.

Only 2 of 14 individuals who had discontinued dupilumab given adverse reactions discontinued lebrikizumab therapy due to similar issues. Additionally, none of those with facial dermatitis, eye-related problems, or inflammatory arthritis on dupilumab reported such events with lebrikizumab.

"These data showed that (lebrikizumab) improved skin symptoms and reduced itch for the majority of patients who had stopped using dupilumab and complement previously presented (lebrikizumab) data in biologic-naive patients, further supporting that a broad range of patients could benefit from this new and effective treatment option,” Stein Gold said in a statement.¹

References

1. ^{Lilly's EBGLYSS™ (lebrikizumab-lbkz) demonstrated meaningful improvement in skin clearance and itch relief in the majority of patients with moderate-to-severe atopic dermatitis who discontinued dupilumab. Eli Lilly and Company. October 25, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-ebglysstm-lebrikizumab-lbkz-demonstrated-meaningful. Date accessed: October 25, 2024.}
2. ^{Silverberg J, et al. Lebrikizumab improves atopic dermatitis and quality of life in patients with moderate-to-severe atopic dermatitis previously treated with dupilumab: Results from the ADapt Trial. 2024 Fall Clinical Dermatology Conference. October 25, 2024.}