Lebrikizumab With Topical Corticosteroid Meets Primary Endpoints for Atopic Dermatitis

Eli Lilly says the drug in combination with TCS also achieved all key secondary endpoints versus the placebo for individuals with AD.

Lebrikizumab significantly improved disease severity when combined with topical corticosteroids (TCS) for individuals with moderate-to-severe atopic dermatitis (AD) in the ADhere phase 3 trial, Eli Lilly and Co said in a statement.

By week 16, the drug met all primary and key secondary endpoints for individuals on the lebrikizumab combination arm.

Lebrikizumab is an IL-13 inhibitor, and it has high bioavailability, a long half-life, and blocks IL-13 signaling.

The IL-13 protein is a central pathogenic mediator in AD and is overexpressed in individuals with AD, driving multiple aspects of AD pathophysiology by promoting T-helper type 2 cell inflammation and resulting in skin barrier dysfunction, flares, infection, itch, and hard, thickened areas of the skin.

"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,” Eric Simpson, MD, MCR, professor of dermatology and director of clinical research at Oregon Health and Science University in Portland, said in the statement.

The primary endpoints were, at week 16, an Investigator Global Assessment score of clear (0) or almost clear (1) skin with a reduction of at least 2 points from baseline and at last a 75% change from baseline in the Eczema Area and Severity Index (EASI) score.

Lebrikizumab in combination with TCS also achieved all key secondary endpoints versus the placebo in combination with TCS for individuals with AD, including improvement in interference of itch on sleep, itch relief, quality of life, and skin improvement.

Key secondary endpoints were measured by the Dermatology Life Quality Index, the EASI, the Pruritus Numeric Rating Scale, and Sleep-Loss due to Pruritus.

Safety results in the 16-week placebo-controlled ADhere study were consistent with the 16-week period of the 2 monotherapy studies in the lebrikizumab phase 3 program for AD.

The most common adverse events for the lebrikizumab-treated group included conjunctivitis and headaches.

"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,” Lotus Mallbris, MD, PhD, vice president of global immunology development and US and global medical affairs at Lilly, said in the statement. “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.”.

Previously, Lilly announced top-line data from ADvocate 1 and ADvocate 2 showing lebrikizumab as a monotherapy met primary and all key secondary endpoints, which included itch during sleep and quality of life at week 16.

Additional data analyses from ADhere, along with results from ADvocate 1 and ADvocate, are planned for future scientific congresses in 2022.

Pending the successful completion of the ongoing ADvocate 1 and ADvocate 2 monotherapy trials, Lilly and Almirall intend to begin European, US, and other regulatory submissions next year.

Reference

Lilly's lebrikizumab demonstrated significant skin improvement and itch relief when combined with topical corticosteroids in people with atopic dermatitis in third Phase 3 study. Lilly. News release. December 21, 2021. Accessed January 4, 2022. https://investor.lilly.com/news-releases/news-release-details/lillys-lebrikizumab-demonstrated-significant-skin-improvement