Lilly's IL-13 Inhibitor Lebrikizumab Plus Topical Corticosteroids Achieves Primary and Secondary Endpoints in Phase 3 ADhere Trial for Moderate-to-Severe Atopic Dermatitis

December 21, 2021 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) recently announced positive topline results from the third Phase 3 clinical trial (ADvocate) of the novel anti-inflammatory drug, IL-13 inhibitor lebrikizumab, for the treatment of moderate to severe atopic dermatitis (AD). The study evaluatedLebrikizumab in combination with topical corticosteroids (TCS) regimenEfficacy and safety. The results showed that at week 16 of treatment,The study met its primary endpoint and all secondary endpoints: the lebrikizumab + TCS regimen significantly improved disease severity, achieved significant skin clearance, alleviated pruritus symptoms, and enhanced quality of life.. These results continue to indicate that,IL-13 Cytokine Inhibition Plays a Key Role in AD Treatment.

In August this year,Eli LillyPositive Topline Results Announced from Two Pivotal Phase 3 Clinical Trials (ADvocate 1, ADvocate 2). These two trials evaluated the efficacy and safety of lebrikizumab as a monotherapy. The results showed that at week 16 of treatment, both studies met the primary endpoint and all secondary endpoints, including skin clearance, itch relief, and quality of life. Data indicated that over half of the patients achieved ≥75% improvement in skin clearance as assessed by EASI.

Lebrikizumab is a novel monoclonal antibody (mAb) that binds to soluble IL-13 with high affinity, featuring high bioavailability, a long half-life, and the ability to block IL-13 signal transduction.Previously, the United StatesFDALebrikizumab has been granted Fast Track Designation (FTD) for the treatment of adult and adolescent patients (12 years to under 18 years, weighing ≥40 kg) with moderate to severe AD.Eli LillyHolds the exclusive rights for the development and commercialization of lebrikizumab in countries outside the United States and Europe. Almirall has been granted the rights to develop and commercialize lebrikizumab in Europe for dermatological indications, including AD.

Atopic Dermatitis (AD), also known as Atopic Eczema, is a chronic inflammatory skin disease caused by skin barrier dysfunction and immune response imbalance. Patients with AD often report intense and persistent itching, which is very uncomfortable and can affect sleep, daily activities, and social relationships.In AD patients, the IL-13 protein (the central pathogenic mediator of the disease) is overexpressed, driving multiple aspects of AD pathophysiology by promoting helper T cell 2 (Th2) cell inflammation, leading to skin barrier dysfunction, pruritus, infection, and hardening and thickening of the skin areas.

Eric Simpson, principal investigator of the ADhere study and professor of dermatology at Oregon Health & Science University, stated: "The treatment of atopic dermatitis is often complex and challenging because many patients need help controlling their symptoms, and the use of steroids alone is insufficient. The overall efficacy and safety data suggest the potential of lebrikizumab as both a monotherapy and combination therapy, addressing unmet needs and improving care for patients suffering from persistent itching and skin inflammation caused by AD, which is encouraging."

Eli LillyImmunologyLotus Mallbris, M.D., Ph.D., Vice President of Development, stated: "Given the heterogeneity of the disease and the varying outcomes of patients' signs and symptoms, doctors treating atopic dermatitis continue to need new options as well as current standards of care for their patients. These results demonstrate the robust Phase 3Clinical TrialThe project has provided increasing evidence and supported the following hypothesis: Targeting the IL-13 pathway is crucial for treating AD and helping improve the prognosis of these patients. We look forward to continuing to evaluate the clinical utility of lebrikizumab in ongoing research and hope to make this drug available to populations whose medical needs remain unmet."

Mechanism of Action of Lebrikizumab (Click image to enlarge, Source: mosmedpreparaty.ru)

ADvocate is a 16-week, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study designed to evaluate lebrikizumab in combination with topical corticosteroids (TCS) for the treatment of adult and adolescent patients (aged 12 to under 18 years, weighing at least 40kg) with moderate to severe atopic dermatitis (AD). In this study, patients' AD symptoms were not adequately controlled with TCS treatment, with or without topical calcineurin inhibitors (TCI).

The primary efficacy endpoint was assessed at Week 16: Investigator's Global Assessment (IGA) of complete clearance of skin lesions (IGA score of 0) or almost complete clearance (IGA score of 1) with an improvement of ≥2 points from baseline, and a ≥75% improvement in the Eczema Area and Severity Index (EASI) score from baseline.

In the study, compared with placebo+TCS, lebrikizumab+TCS achieved the primary endpoint. Additionally, compared with placebo+TCS, lebrikizumab+TCS also achieved all key secondary endpoints, including: improvement in skin clearance, relief of itching, reduction in sleep interference due to itching, and improvement in quality of life. The key secondary endpoints were measured using EASI, Pruritus Numerical Rating Scale (PNRS), Sleep-Loss due to Pruritus, and Dermatology Life Quality Index (DLQI).

In the 16-week placebo-controlled ADhere study, safety outcomes were consistent with the 16-week results from two monotherapy studies (ADvocate 1, ADvocate 2) in the lebrikizumab Phase 3 program for AD. The most common adverse events in patients treated with lebrikizumab were conjunctivitis and headache.

Additional data analysis of the ADhere study, as well as the results of the ADvocate 1 and ADvocate 2 studies, will be presented at medical conferences in 2022.MeetingPublished above. These studies are part of the lebrikizumab Phase 3 program, which includes five pivotal, ongoing global studies, including two monotherapy studies (ADvocate 1, ADvocate 2) and one combination study (ADhere), as well as a long-term extension (ADjoin) and an open-label adolescent trial (ADore). Upon the successful completion of the ongoing ADvocate 1 and ADvocate 2 studies,Eli LillyAlmirall plans to submit lebrikizumab for the treatment of moderate to severe AD to U.S., EU, and other regulatory authorities in 2022. (Bioon.com)

Source of Original Text: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