Lilly's Lebrikizumab Performs Well in Two Phase 3 AD Trials

Lebrikizumab significantly improved skin clearance and itch in people with moderate-to-severe atopic dermatitis in two Phase 3 trials.

Eli Lilly and Company's lebrikizumab led to significant improvements with at least 75 percent skin clearance in more than half of people with moderate-to-severe atopic dermatitis (AD), according to top-line results from ADvocate 1 and ADvocate 2.

All primary and all key secondary endpoints, including skin clearance and itch improvement, were met at Week 16, the studies showed.

Lebrikizumab is a novel monoclonal antibody (mAb) that binds soluble IL-13 with high affinity, has high bioavailability, a long half-life and blocks IL-13 signaling.  The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to lebrikizumab for moderate-to-severe AD in adult and adolescent patients (aged 12 to less than 18 years of age and weighing at least 40 kg). 

"AD is a heterogenous disease with signs and symptoms varying greatly between patients, underscoring the need for additional treatment options with different mechanisms of action," says Jonathan Silverberg, M.D., Ph.D., M.P.H., associate professor of dermatology at George Washington University School of Medicine and Health Sciences in Washington, DC, and a principal investigator of the ADvocate 2 trial, in a news release. "Data from the studies showed lebrikizumab's effect on skin clearance and its potential to address a key driver for this disease as well as provide improvements in itch, sleep disturbance and quality of life."

ADvocate 1 and ADvocate 2 are ongoing 52-week randomized, double-blind, placebo-controlled, parallel-group, Phase 3 studies designed to evaluate lebrikizumab as monotherapy in adult and adolescent patients (aged 12 to less than 18 years of age and weighing at least 40 kg) with moderate-to-severe AD. The primary efficacy endpoints were assessed at 16 weeks in the two studies and were measured by an Investigator Global Assessment (IGA) score of clear (0) or almost clear (1) skin with a reduction of at least two points from baseline at Week 16 and at least a 75 percent or greater change from baseline in their Eczema Area and Severity Index (EASI) score at Week 16.

Lebrikizumab also achieved key secondary endpoints versus placebo in patients with AD, including early onset in skin clearance and itch relief, improvement in interference of itch on sleep and quality of life. Key secondary endpoints were measured by the IGA, EASI, the Pruritus Numeric Rating Scale, Sleep-Loss due to Pruritus and the Dermatology Life Quality Index.

In the initial 16-week placebo-controlled period of ADvocate 1 and ADvocate 2, the incidence of treatment-emergent adverse events (AEs) and serious AEs among patients treated with lebrikizumab was consistent with that of the previous Phase 2 lebrikizumab study in AD. The most common AEs included conjunctivitis, nasopharyngitis and headache for lebrikizumab-treated patients. Discontinuations due to AEs were similar in the lebrikizumab group (1.4%) compared to placebo (1.7%).

"We understand the needs of people in the AD community worldwide and are aware that many are still in need of new treatment options despite available medicines," says Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly. "Lebrikizumab is a specific inhibitor of IL-13 that offers robust binding affinity and high bioavailability. Today's results show that the inhibition of IL-13 cytokine plays a main role in AD treatment, as demonstrated by more than half of the patients achieving at least 75% clearance to total clearance on lebrikizumab monotherapy."

The full study results from ADvocate 1 and ADvocate 2 will be disclosed at future congresses in 2022. Data from a Phase 3 combination study (ADhere) of lebrikizumab with topical corticosteroids in patients with AD will be available later this year. These studies are part of the lebrikizumab Phase 3 program, which consists of five key ongoing, global studies including two monotherapy studies and a combination study as well as long-term extension (ADjoin) and adolescent open label (ADore) trials.

"We are excited about the data received from the studies that support lebrikizumab's potential efficacy in AD and by the prospect of delivering this promising therapy to people living with moderate-to-severe AD in Europe," states Karl Ziegelbauer, Ph.D., 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.