Lebrikizumab (Ebglyss; Lilly) has demonstrated significant efficacy in treating moderate to severe atopic dermatitis (AD), including in patients who have previously discontinued dupilumab (Dupixent; Sanofi and Regeneron). The anti-IL-13 monoclonal antibody, approved by the FDA on September 13, 2024, offers a targeted approach to managing the chronic inflammatory skin condition.
FDA Approval and Mechanism of Action
Lebrikizumab is indicated for adults and children aged 12 years and older, weighing at least 40 kg, with moderate to severe AD who have not responded adequately to topical prescription therapies. It functions by specifically targeting interleukin-13 (IL-13), a key cytokine involved in Type 2 inflammation, which plays a crucial role in the pathogenesis of atopic dermatitis. By blocking IL-13 signaling, lebrikizumab inhibits downstream pro-inflammatory responses, reducing symptoms such as redness, inflammation, and itching.
Clinical Trial Data
The FDA approval was supported by data from the ADvocate 1 (NCT04146363), ADvocate 2 (NCT04178967), and ADhere (NCT04250337) studies. These trials included over 1000 adults and children aged 12 years and older with moderate to severe eczema that was unresponsive to topical treatments.
In the ADvocate 1 and ADvocate 2 trials, 38% of participants treated with lebrikizumab achieved clear or almost clear skin at 16 weeks, compared to 12% in the placebo group. Notably, 10% of participants saw results within 4 weeks. Among those who achieved clear or almost clear skin at week 16, 77% maintained this outcome for a year with monthly dosing. Furthermore, 43% of participants reported itch relief at 16 weeks with lebrikizumab, compared to 12% on placebo, with 85% maintaining relief at 1 year with monthly dosing. These results were published in the New England Journal of Medicine.
The ADhere trial, a 16-week study, evaluated lebrikizumab in combination with topical corticosteroids, demonstrating the efficacy and safety of this combination therapy.
Efficacy After Dupilumab Discontinuation
Lilly announced results from the Phase 3b ADapt study at the 2024 Fall Clinical Dermatology Conference, which evaluated the efficacy of lebrikizumab in patients with moderate to severe AD who had previously been treated with dupilumab. The study enrolled 86 patients aged 12 years and older who had an inadequate response to dupilumab or experienced intolerable side effects.
The results indicated that 83% of patients with a baseline Dermatology Life Quality Index (DLQI) score of 4 or higher achieved at least a 4-point improvement by weeks 16 and 24. Additionally, among those with a baseline pruritus numerical rating scale score of 4 or higher, 53% and 62% reported significant reductions in itch severity at weeks 16 and 24, respectively.
Mark Genovese, MD, senior vice president of Lilly Immunology development, stated that the trial reinforces that Ebgylss provided a meaningful benefit among individuals who have already tried another biologic treatment such as dupilumab and may have more difficult-to-treat disease.
Dosing and Administration
Lebrikizumab is administered via subcutaneous injection. The initial dose is 500 mg at Weeks 0 and 2, followed by 250 mg every 2 weeks until week 16 or later. Once an adequate clinical response is achieved, patients transition to a maintenance dose of 250 mg every 4 weeks. Injection sites include the abdomen, thigh, and back of the upper arm, avoiding areas affected by atopic dermatitis.
Safety Profile
Common adverse reactions include conjunctivitis, injection site reactions, and herpes zoster. The use of live vaccines should be avoided during treatment with lebrikizumab. The majority of adverse events reported in the ADapt study were mild to moderate in severity, with a small number leading to treatment discontinuation.
Contraindications and Special Populations
Lebrikizumab is contraindicated in individuals with known hypersensitivity to the product. Caution is advised in pregnant women, and there is limited data on its presence in human milk. The safety and effectiveness have been established in pediatric patients 12 years and older, weighing at least 40 kg, with moderate to severe atopic dermatitis inadequately controlled with topical therapies.
