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At weeks 16 and 24, approximately 57% and 60% of patients with moderate to severe atopic dermatitis, respectively, achieved at least 75% improvement in Eczema Area and Severity Index score.
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According to findings from the phase 3b clinical trial ADapt (NCT05369403), lebrikizumab (Ebglyss; Eli Lilly and Co) improved skin—including hand and face—and itch among patients with moderate to severe atopic dermatitis who were previously treated with dupilumab (Dupixent; Sanofi, Regeneron). Further results were shared at the 2024 Fall Clinical Dermatology Conference, which was held in Las Vegas, Nevada from October 24 to 27.1
Lebrikizumab is an interleukin (IL)-13 inhibitor that selectively blocks IL-13 signaling with high binding affinity. In atopic dermatitis, the cytokine IL-13 is key in driving the type 2 inflammatory cycle in the skin, which leads to skin barrier dysfunction and symptoms such as itch, thickening of the skin, and infection. Lebrikizumab was approved by the FDA in September 2024 for adults and children 12 years and older who weigh at least 88 pounds (40 kg) with moderate to severe atopic dermatitis that is not well-controlled with topical prescription therapies.1
“Treatment isn't 1-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,” said study investigator Linda Stein Gold, MD, director of dermatology research and head of the Division of Dermatology for Henry Ford Health System in Detroit, Michigan, in a news release.1
ADapt (NCT05369403) is an open-label, 24-week phase 3b clinical trial that evaluated the efficacy and safety of lebrikizumab in adults and adolescents (12 to <18 years of age) who weigh 40 kg or more with moderate to severe atopic dermatitis who previously received dupilumab as a treatment. After 4 or more weeks of dupilumab discontinuation, patients were treated with a starting dose of lebrikizumab (500 mg, two 250-mg injections) at week 0 and week 2, followed by 250 mg every 2 weeks until week 16.1,2
Further, patients with an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin, or patients with at least 75% improvement of Eczema Area and Severity Index (EASI-75) score at week 16 received 250 mg once monthly. Non-responders continued receiving 250 mg every 2 weeks until week 24. Additionally, patients were allowed to stay on low and mid-potency topical corticosteroids.1,2
Trial Name: A Study of Lebrikizumab (LY3650150) in Adult and Adolescent Participants With Moderate-to-Severe Atopic Dermatitis Previously Treated With Dupilumab (ADapt)
ClinicalTrials.gov ID: NCT05369403
Sponsor: Eli Lilly and Company
Completion Date: January 11, 2024
The study’s primary end point was at least 75% improvement in EASI-75 score at the 16-week period. Secondary end points at weeks 16 and 24 included IGA score of 0 or 1 and a reduction of at least 2 points from baseline, and at least a 4-point improvement in Pruritus NRS from baseline. Additional secondary and exploratory end points were also included.1,2
According to the study findings, approximately 57% of patients at week 16 and 60% of patients at week 24, respectively, achieved an EASI-75. These results, according to the investigators, are similar to those observed in phase 3 monotherapy trials—ADvocate 1 (NCT04146363) and ADvocate 2 (NCT04178967)—that evaluated lebrikizumab in patients without prior exposure to dupilumab.1
Further, around 53% and 62% of patients in the ADapt trial had also experienced itch relief, with at least a 4-point improvement from baseline at weeks 16 and 24, respectively. Additionally, patients also saw improvements in difficult-to-treat areas, with approximately 52% seeing clear or almost clear face dermatitis at week 24. Among patients with moderate to severe hand dermatitis at baseline, their modified total lesion symptom score decreased by 75% at week 24.1
“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,” said Stein Gold in the news release.1
According to the investigators, less than 6% of patients treated with lebrikizumab reported adverse events (AEs) that led to treatment discontinuation. Among the 14 patients who discontinued dupilumab because of AEs (10 patients experienced eye-related events, facial dermatitis, or inflammatory arthritis), 2 patients lebrikizumab because of an AE. These were not similar to the AEs that led to dupilumab discontinuation.1
In addition, the safety profile of lebrikizumab was shown to be consisted with prior lebrikizumab phase 3 trials in patients with moderate to severe atopic dermatitis, with no new safety signals observed. All AEs were considered mild or moderate in severity, and the most common treatment-related AEs were conjunctivitis and injection site reactions.1
“This trial supports the growing body of data showing that health care providers can have confidence prescribing [lebrikizumab] as a first-line biologic treatment for moderate to severe atopic dermatitis, and reinforces that [lebrikizumab] provided a meaningful benefit among individuals who have already tried another biologic treatment such as dupilumab and may have more difficult-to-treat disease,” said Mark Genovese, MD, senior vice president of Lilly Immunology development, in the news release.1
