Lebrikizumab, an IL-13 inhibitor, significantly improved disease severity when combined with topical corticosteroids (TCS) in people with moderate-to-severe atopic dermatitis (AD) in Eli Lilly and Company's third pivotal Phase 3 trial (ADhere). By Week 16, the study met all primary and key secondary endpoints for patients on the lebrikizumab combination arm.

Lebrikizumab is a novel, investigational monoclonal antibody (mAb) that binds soluble IL-13 with high affinity, has high bioavailability, a long half-life and blocks IL-13 signaling.1-5 In people with AD, the IL-13 protein—a central pathogenic mediator in the disease—is overexpressed, driving multiple aspects of AD pathophysiology by promoting T-helper type 2 (Th2) cell inflammation and resulting in skin barrier dysfunction, itch, infection, flares and hard, thickened areas of skin.6,7

"AD is often complex and challenging to treat, as many patients need help controlling their symptoms when topical steroids alone are not enough," says Eric Simpson, MD, MCR, Professor of Dermatology and Director of Clinical Research at Oregon Health & Science University in Portland and a principal investigator of the ADhere study. "I'm encouraged by the aggregate efficacy and safety data which have demonstrated the potential for lebrikizumab as both monotherapy and combination therapy to address unmet needs and improve care for people living with persistent itch and inflamed skin caused by AD."

The primary endpoints were Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction of at least two points from baseline and at least a 75 percent change from baseline in the Eczema Area and Severity Index (EASI) score, both at Week 16. Lebrikizumab in combination with TCS also achieved all key secondary endpoints versus placebo in combination with TCS in patients with AD, including skin improvement, itch relief, improvement in interference of itch on sleep, and quality of life. Key secondary endpoints were measured by EASI, the Pruritus Numeric Rating Scale, Sleep-Loss due to Pruritus, and the Dermatology Life Quality Index.

Safety results in the 16-week placebo-controlled ADhere study were consistent with the 16-week period of the two monotherapy studies in the lebrikizumab Phase 3 program for AD. The most common adverse events (AEs) included conjunctivitis and headache for lebrikizumab-treated patients.

In August 2021, Lilly announced top-line data from ADvocate 1 and ADvocate 2 showing lebrikizumab as a monotherapy met primary and all key secondary endpoints including itch, interference of itch on sleep and quality of life at Week 16.

"Physicians treating atopic dermatitis continue to need new options for their patients along with current standard of care, given the heterogeneity of disease and variable outcomes for patients' signs and symptoms," says Lotus Mallbris, MD, PhD, vice president of global immunology development and U.S. and global medical affairs at Lilly. "These results add to the growing body of evidence from our robust Phase 3 clinical trial program for lebrikizumab and support the hypothesis that targeting the IL-13 pathway is critical in treating AD and helping improve outcomes for these patients. We look forward to continuing to evaluate lebrikizumab's clinical utility in the ongoing studies in the hopes of making this medicine available to those who still have unmet needs."

Additional data analyses from ADhere, along with results from two monotherapy Phase 3 trials, ADvocate 1 and ADvocate 2, are planned for future scientific congresses in 2022. Pending successful completion of the ongoing ADvocate 1 and ADvocate 2 monotherapy trials, Lilly and Almirall intend to begin US, EU, and other regulatory submissions next year.

"These results validate the important role that IL-13 cytokine inhibitors play in AD treatment and the success of lebrikizumab in this study represents another key achievement in our journey to offer treatment advances in AD for patients and healthcare professionals," stated Karl Ziegelbauer, PhD, Almirall S.A.'s Chief Scientific Officer.

Lilly has exclusive rights for development and commercialization of lebrikizumab in the United States and 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.