At 16 weeks, 70 percent of patients with moderate-to-severe atopic dermatitis (AD) receiving lebrikizumab combined with topical corticosteroids (TCS) achieved an EASI-75.

Atopic dermatitis patients taking lebrikizumab plus topical steroids showed significant improvements in disease severity, according to study results from the ADhere trial presented at the 4th Annual Revolutionizing Atopic Dermatitis (RAD) Conference.

At 16 weeks, 70 percent of patients with moderate-to-severe atopic dermatitis (AD) receiving lebrikizumab combined with standard-of-care topical corticosteroids (TCS) achieved at least 75 percent improvement in overall disease severity (EASI-75), the study found.

Lebrikizumab is a novel, monoclonal antibody (mAb) that binds to the interleukin 13 (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. In AD, IL-13 underlies the signs and symptoms including skin barrier dysfunction, itch, infection and hard, thickened areas of skin.

Lebrikizumab also showed improvements in itch, sleep interference, and quality of life when combined with TCS, compared to placebo plus TCS.

"Today's ADhere data, together with results from the ADvocate monotherapy studies, demonstrate the potential for lebrikizumab to reduce disease burden and provide relief for people with uncontrolled atopic dermatitis when used either alone or combined with topicals," says Eric Simpson, M.D., M.C.R., Professor of Dermatology and Director of Clinical Research at Oregon Health & Science University in Portland, and principal investigator of Adhere, in a news release. "Lebrikizumab specifically targets the IL-13 pathway, which plays the central role in this chronic inflammatory disease. These results strengthen our understanding of lebrikizumab in atopic dermatitis and help establish it as a possible new treatment option."

Among patients taking lebrikizumab plus TCS, 41 percent achieved clear or almost clear skin (IGA) at 16 weeks compared to 22 percent of patients taking placebo plus TCS. At 16 weeks, 70 percent of patients taking lebrikizumab plus TCS achieved an EASI-75 response compared to 42 percent taking placebo plus TCS. Differences between patients receiving lebrikizumab in combination with TCS and placebo with TCS were observed as early as four weeks for EASI-75.

Patients treated with lebrikizumab plus TCS also achieved statistically significant improvements across key secondary endpoints including skin clearance and itching, interference of itch on sleep, and quality of life measures, compared to placebo with TCS. Clinically meaningful differences were observed as early as four weeks for itch, interference of itch on sleep, and quality of life measures, the study showed.

Safety results were consistent with prior lebrikizumab studies in AD. Patients taking lebrikizumab plus TCS, compared to placebo plus TCS, reported a higher frequency of adverse events (lebrikizumab plus TCS: 43%, placebo plus TCS: 35%). Most adverse events were mild or moderate in severity and nonserious and did not lead to treatment discontinuation. The most common adverse events for those on lebrikizumab were conjunctivitis (5%) and headache (5%).

"Lilly is working to empower people with skin-related diseases, such as atopic dermatitis, to live their lives to the fullest potential," says Lotus Mallbris, M.D., Ph.D., vice president of global immunology development and medical affairs at Lilly. "We recognize the critical need for more options for people whose disease cannot be controlled with topicals. We look forward to seeing full results from our broader Phase 3 program and advancing lebrikizumab worldwide."

Lilly recently announced 16-week data from the ongoing ADvocate studies, and an encore presentation of results was presented at RAD 2022. Additionally, longer term data from the ADvocate studies will be disclosed in coming months.

"These results are a further step in our commitment to deliver innovative therapies that make a meaningful difference to patients. We look forward to announcing exciting new milestones in the months to come," says Karl Ziegelbauer, Ph.D., Almirall S.A.'s Chief Scientific Officer.

About lebrikizumab

Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and the rest of the world outside Europe. Almirall has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe.

The U.S. Food and Drug Administration (FDA) granted lebrikizumab Fast Track designation in AD in December 2019. The lebrikizumab Phase 3 program consists of five key global studies including two monotherapy studies (ADvocate 1 and 2), a combination study (ADhere), as well as long-term extension (ADjoin) and adolescent open label (ADore) studies.

About ADhere 

ADhere is a 16-week randomized, double-blind, placebo-controlled, parallel-group, global, Phase 3 study to evaluate the efficacy and safety of lebrikizumab in combination with TCS initiated in 211 adult and adolescent patients (aged 12 to less than 18 years of age and weighing at least 40 kg) with moderate-to-severe AD. In the study, patients' AD symptoms were inadequately controlled by TCS with or without topical calcineurin inhibitors (TCI). The study was designed to be more reflective of clinical practice and patients were provided with mid-potency TCS (triamcinolone acetonide 0.1% cream), and low-potency TCS (hydrocortisone 1% cream, for use on sensitive skin areas) which could be tapered, stopped or resumed at the patient's discretion.

The primary endpoints were measured by an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction from baseline and at least 75 percent change in baseline in the Eczema Area and Severity Index (EASI-75) score at 16 weeks. EASI measures extent and severity of the disease. Key secondary endpoints were measured by EASI, the Pruritus Numeric Rating Scale, Sleep-Loss due to Pruritus and the Dermatology Life Quality Index.