In the third phase 3 study in patients with atopic dermatitis, lebrikizumab, when combined with topical corticosteroids, showed significant improvement in skin and relief from itching

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  • Study met all primary and major secondary endpoints

  • Safety profile consistent with previous studies of lebrikizumab in atopic dermatitis

  • Global submissions are expected to be submitted next year based on data from the Phase 3 clinical trial program

Barcelona, ​​Spain, December 21, 2021 / PRNewswire / – Lebrikizumab, an IL-13 inhibitor, improved disease severity in combination with topical corticosteroids (TCS) in people with moderate to severe atopic dermatitis in a third pivotal Phase 3 study (ADhere) announced today ( AD) significant. through Almirall SA (BME: ALM). By Week 16, the study met all primary and major secondary endpoints for patients in the lebrikizumab combination arm.

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Lebrikizumab is a novel monoclonal antibody (mAb) under investigation that binds soluble IL-13 with high affinity, has high bioavailability, has a long half-life, and blocks IL-13 signaling.1-5 In people with AD, the IL-13 protein – a key pathogenic mediator of the disease – is overexpressed, which drives several aspects of AD pathophysiology by promoting inflammation of type 2 (Th2) T helper cells and becoming one Skin barrier dysfunction, itching and infection results in flares and hard, thickened areas of skin.6.7

“The signs and symptoms of AD vary based on individual patient characteristics and, depending on the severity, can affect their sleep, social activities, and general well-being. Patients need effective and well-tolerated treatment options that provide long-term disease control and an optimal quality of life, ” said Dr. med. Andreas Pinter, Director of Clinical Research at the University Hospital in Frankfurt / Main (Germany) and one of the investigators in the ADhere trial. “Lebrikizumab recently demonstrated its potential as monotherapy. ADhere’s data now also showed its effects on skin healing and itching relief in combination therapy, suggesting that the drug could become a new treatment option for this immune-mediated chronic skin condition. “

The primary endpoints were the 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 in eczema area and severity index from baseline (EASI) score, both at Week 16. Lebrikizumab in combination with TCS also met all major secondary endpoints compared to placebo, including skin improvement, itch relief, improvement in itching impairment to sleep, and quality of life in patients with AD. The key secondary endpoints were measured using EASI, the Numeric Rating Scale for Pruritus, Sleep Loss Due to Pruritus, and the Dermatology Life Quality Index.

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

In August 2021, Top-line data from ADvocate 1 and ADvocate 2 were announced by Almirall showing that lebrikizumab as monotherapy met primary and all major secondary endpoints including pruritus, itchy sleep impairment, and quality of life at week 16.

We are pleased again with the robust data on lebrikizumab that we have received so far, both as monotherapy, as presented in the 16-week data readout of the ADvocate 1 and 2 studies last August, or in combination with corticosteroids, as the results of the announced today Phase 3 clinical trial ADhere. These results confirm the important role that IL-13 cytokine inhibitors play in the treatment of AD. The success of lebrikizumab in this study marks another major achievement in our journey to provide advances in AD treatment to patients and healthcare professionals seeking new options to address unmet need“Said Karl Ziegelbauer, Ph.D., Chief Scientific Officer of Almirall SA.

ADhere’s detailed results, along with data from two phase 3 monotherapy studies, ADvocate 1 and ADvocate 2, are planned for future scientific congresses in 2022. Pending the successful completion of the ongoing ADvocate 1 and ADvocate 2 monotherapy trials, Almirall and Eli Lilly and The Company intends to begin filing EU, US and other regulatory filings next year.

“These results complement the growing evidence from our robust Phase 3 clinical trial program. We look forward to our continued partnership with Almirall to advance our global regulatory plans in the hope of making lebrikizumab available to those who have unmet needs. “ said Lotus Mallbris, MD, Ph.D., Vice President of Global Immunology Development and US and Global Medical Affairs at Lilly.

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

About ADhere and the Phase 3 program

ADhere is a 16-week, randomized, double-blind, placebo-controlled, phase 3, parallel-group study evaluating the efficacy and safety of lebrikizumab in combination with TCS in adult and adolescent patients (aged 12 to under 18 years). 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 (TCIs).

The U.S. Food and Drug Administration (FDA) has given lebrikizumab fast-track status in AD in. granted December 2019. Lebrikizumab’s Phase 3 program consists of five ongoing, global main studies, including two monotherapy studies and today’s ADhere combination study, as well as long-term extension studies (ADjoin) and open youth studies (ADore).

About eczema

Atopic dermatitis (AD), or atopic eczema, is a chronic, recurrent skin condition characterized by severe itching, dry skin, and inflammation that can appear on any part of the body.8th AD is a heterogeneous disease, both biologically and clinically, and can be characterized by a wide variety of symptoms, with relapses occurring in unpredictable ways.9

Moderate to severe AD is characterized by intense itching, which leads to an itch-scratch cycle that further damages the skin.10 Like other chronic inflammatory diseases, AD is immune-mediated and involves a complex interplay of immune cells and inflammatory cytokines.8th People living with AD often report symptoms of intense, persistent itching, which can be so uncomfortable that it can affect sleep, daily activities, and social relationships.

About lebrikizumab

Lebrikizumab is a novel monoclonal antibody under investigation that is designed to bind IL-13 with high affinity to specifically prevent the formation of the IL-13Rα1 / IL-4Rα heterodimer complex and subsequent signaling, whereby the biological effects of IL-13 are specifically inhibited and efficient fashion. IL-13 is a key pathogenic mediator that powers several aspects of the pathophysiology that underlie the signs and symptoms of AD by promoting type 2 inflammation and mediating its effects on tissues, resulting in skin barrier dysfunction, Itching, skin thickening, and infection results.6th

1 Moyle M. et al. Exp dermatol. 2019; 28 (7): 756-768.
2 Ultsch M. et al. J. Mol. Biol. 2013; 425 (8): 1330-1339.
3 R. Zhu et al. Pulm Pharmacol There. 2017; 46: 88-98.
4th Simpson EL, et al. J Am Acad Dermatol. 2018; 78 (5): 863-871.e11.
5 Okragly A, et al. Comparison of the affinity and in vitro activity of lebrikizumab, tralokinumab and cendakimab. Presented on the inflammatory skin disease Summit, New York, 3rd-6th November 2021.
6th Beaver T. allergy. 2020; 75 (1): 54-62.
7th Ungar B, et al. J Invest Dermacol. 2017; 137 (3): 603-613.
8th Weidinger S, Novak N. lancet. 2016; 387: 1109-1122.
9 Langan SM et al. Bow dermatol. 2008; 142: 1109.
10 Yosipovitch G, et al. Curr Allergy Representative. 2008; 8: 306-311.

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