– BARCELONA, Aug. 16, 2021 /PRNewswire/ — 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), as measured by EASI*, in ADvocate 1 and ADvocate 2 Phase 3 clinical trials announced today by Almirall S.A. (BME: ALM). In the top-line results from these two monotherapy studies, primary and all key secondary endpoints, including skin clearance and itch improvement, were met at Week 16. 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.1-4 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). Fast Track designation is granted for a medicine that is intended to treat a serious condition and data demonstrate the potential to address an unmet medical need.

AD, also known as atopic eczema, is a chronic inflammatory skin disorder caused by skin barrier dysfunction and dysregulation of the immune response. People living with AD often report symptoms of intense, persistent itch which can be so uncomfortable that it can affect sleep, daily activities and social relationships. 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 and hard, thickened areas of skin.5,6

“AD is an immune-mediated chronic skin condition with a significant impact on the wellbeing and quality of life of patients. Despite recent treatment advances there remains a high unmet need for medicines that provide effective and well tolerated treatment options,” said Prof. Dr. med. Diamant Thaçi, Director at the Comprehensive Centre for Inflammation Medicine at the University of Lübeck in Germany, and principal investigator of the ADvocate 2 trial. “Data from these pivotal studies showed significant improvements on skin clearance and itch combined with a reassuring safety profile, making it potentially a valuable addition to the therapeutic armamentarium.”

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 are excited about the data received from the studies that support lebrikizumab’s potential efficacy in AD and show that the inhibition of IL-13 cytokine plays a main role in AD treatment. These results validate our commitment to the dermatology community and support our vision of offering truly meaningful and new treatment advances to people living with chronic, life-altering skin conditions. We look forward to continuing our collaboration with Eli Lilly and Company on the lebrikizumab clinical development program and are excited by the prospect of delivering this promising therapy to people living with moderate-to-severe AD in Europe,” stated Karl Ziegelbauer, Ph.D Almirall’s Chief Scientific Officer.

“Today marks an important milestone in our clinical development program for lebrikizumab, a medicine we believe has the potential to be best-in-class for IL-13 treatment, and reaffirms our steadfast commitment to the dermatology community worldwide,” said Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly.

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

About Advocate1 and Advocate2

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 Week 16 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.

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.

About Atopic Dermatitis

Atopic dermatitis (AD), or atopic eczema, is a chronic, relapsing skin disease characterized by intense itching, dry skin and inflammation that can be present on any part of the body.7 AD is a heterogeneous disease both biologically and clinically, and may be characterized by a highly variable appearance in which flares occur in an unpredictable manner.8

Moderate-to-severe AD is characterized by intense itching, which leads to an itch-scratch cycle that further damages the skin.9 Like other chronic inflammatory diseases, AD is immune-mediated and involves a complex interplay of immune cells and inflammatory cytokines.7

About Lebrikizumab

Lebrikizumab is a novel, investigational, monoclonal antibody designed to bind IL-13 with high affinity to specifically prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13 in a targeted and efficient fashion. IL-13 is believed to be a central pathogenic mediator that drives multiple aspects of the pathophysiology underlying the range of signs and symptoms of AD by promoting type 2 inflammation and mediating its effects on tissue, resulting in skin barrier dysfunction, itch, skin thickening and infection.

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 Zhu R, et al. Pulm Pharmacol Ther. 2017;46:88-98.

4 Simpson EL, et al. J Am Acad Dermatol. 2018;78(5):863-871.e11.

5 Bieber T. Allergy. 2020;75(1):54-62.

6 Ungar B, et al. J Invest Dermatol. 2017;137(3):603-613.

7 Weidinger S, Novak N. Lancet. 2016;387:1109-1122.

8 Langan SM, et al. Arch Dermatol. 2008;142:1109.

9 Yosipovitch G, et al. Curr Allergy Rep. 2008;8:306-311.

[*] Eczema Area and Severity Index

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