The monotherapy demonstrates rapidly improved symptoms over 4 weeks for individuals with moderate-to-severe disease.
More than 50% of patients with moderate-to-severe atopic dermatitis (AD) showed at least 75% reduction in disease severity (EASI-75*) at 16 weeks when receiving lebrikizumab monotherapy in the ADvocate program, Eli Lilly and Company said at the American Academy of Dermatology’s Annual Meeting taking place March 25 to 29, 2022.
Lebrikizumab, an investigational interleukin (IL)-13 inhibitor, also led to clinically meaningful improvements in itching and other important patient-reported outcomes compared with the placebo.
“Patients with atopic dermatitis experience persistent itch, dry skin, severe pain and inflammation, which can be unpredictable and affect their work, social relationships, mental and emotional health,” Emma Guttman-Yassky, MD, PhD, Waldman professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York, and senior author of the ADvocate analyses, said in a statement.
“Lebrikizumab is a novel treatment targeting the IL-13 pathway, which is the main cytokine driver of inflammation that is involved in AD,” she said. “I'm encouraged by today's data showing rapid improvements in skin, itch, and quality-of-life measures.”
Lebrikizumab is a monoclonal antibody (mAb) that binds to the IL-13 protein with high affinity to specifically prevent the formation of IL-13Rα1/IL-4Rα (type 2 receptor) which blocks downstream signaling through the IL-13 pathway. IL-13 plays the central role in type 2 inflammation. In AD, IL-13 underlies the signs and symptoms, including hard and thickened areas of skin, infection, itch, and skin barrier dysfunction.
In the ADvocate 1 study, 43% of patients receiving lebrikizumab achieved clear or almost clear skin at 16 weeks compared with 13% taking the placebo. Among those receiving lebrikizumab, 59% achieved an EASI-75 response compared with 16% with the placebo.
In the ADvocate 2 study, 33% of patients taking lebrikizumab achieved clear or almost clear skin at 16 weeks compared with 11% taking the placebo. Among those receiving lebrikizumab, 51% achieved an EASI-75 response compared with 18% with the placebo.
Within 4 weeks, patients receiving lebrikizumab experienced statistically significant improvements in skin clearance and itching, as well as improvements in interference of itching on quality of life and sleep, as measured by key secondary endpoints.
The safety profile of the 16-week period was consistent with prior lebrikizumab studies in AD. Compared with those taking the placebo, patients taking lebrikizumab reported a lower frequency of adverse events (AEs) in ADvocate 1 (45% for lebrikizumab and 52% for the placebo) and ADvocate 2 (53% for lebrikizumab and 66% for the placebo). Most AEs across the 2 studies were mild or moderate in severity and did not lead to treatment discontinuation. The most common AEs in ADvocate 1 and 2 for those on lebrikizumab were conjunctivitis, common colds, and headaches.
Lilly will disclose detailed 52-week results from ADvocate 1 and 2, as well as 16-week data from ADhere, the phase 3 AD study of lebrikizumab with topical steroids, in the coming months, the company said in the statement.
Lilly and Almirall S.A. plan to submit filings to regulatory authorities around the world by the end of 2022, following completion of the ADvocate studies.
Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of world outside Europe. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe.
Majority of patients treated with lebrikizumab achieved skin clearance in Lilly's pivotal phase 3 atopic dermatitis studies. Eli Lilly and Company. News release. March 26, 2022. Accessed March 28, 2022. https://investor.lilly.com/news-releases/news-release-details/majority-patients-treated-lebrikizumab-achieved-skin-clearance