LEO Pharma Reveals Phase 2a Trial Results of Temtokibart and Dupilumab in Atopic Dermatitis at 2024 EADV Meeting

BALLERUP, Denmark I September 26, 2024 I LEO Pharma A/S, a prominent player in the field of medical dermatology, has revealed promising findings from its Phase 2a Mechanism of Action (MoA) trial. This study evaluated the mechanistic effects of the investigational drugs temtokibart and dupilumab in individuals suffering from moderate-to-severe atopic dermatitis (AD). The results were presented as a Late Breaker oral presentation at the 2024 EADV Annual Meeting.

The Phase 2a MoA trial focused on the impacts of inhibiting the IL-22RA1 and interleukin 4 receptor alpha (IL-4Rα) in patients with moderate-to-severe AD. According to the findings, temtokibart administered at 450 mg biweekly (Q2W, n=8) significantly enhanced skin hydration more quickly and effectively than dupilumab at 300 mg Q2W (n=4). Notably, temtokibart demonstrated a significant improvement in natural moisturizing factors PCA and UCA by the first week from baseline (p<0.0001). Additionally, improvements in barrier function markers, including terminal differentiation markers and cell adhesion molecules, were observed with temtokibart treatment.

As anticipated from its MoA, dupilumab exhibited a substantial and consistent reduction in Type 2-associated inflammatory markers, especially in immune cells and fibroblasts. Clinical improvements in EASI and itch NRS from baseline to Week 16 were comparable between temtokibart and dupilumab. These findings suggest that IL-22RA1 blockade does not directly influence skin immune cells but can promptly correct barrier abnormalities, indicating a potentially new MoA for patients with moderate-to-severe AD.

Dr. Christine Bangert, MD, who serves as the Head of the Allergology Task Force of the Austrian Society of Dermatology and Venereology and leads the atopic eczema outpatient clinic at the Medical University of Vienna, was the Principal Investigator for the Phase 2a MoA trial. She remarked, “The results of this trial provide new insights into the pathophysiology of AD and give us a unique understanding of the mode of action of temtokibart. These data suggest that the IL-22 pathway is central to atopic dermatitis pathogenesis, demonstrating that Type 2 inflammation is not the only relevant driver of the disease.”

Temtokibart is an investigational monoclonal antibody currently undergoing Phase 2 development for the treatment of moderate-to-severe AD. It functions by blocking the IL-22RA1 receptor subunit, thereby inhibiting the effects of the interleukin-22 (IL-22) cytokine and partially inhibiting IL-20 and IL-24 signaling. A Phase 2b dose-finding trial is also underway to assess the efficacy and safety of various doses of temtokibart in adult patients with moderate-to-severe AD. The recruitment for this trial is complete, and results are anticipated in Q1 2025.

Kreesten Meldgaard Madsen, Chief Development Officer at LEO Pharma, expressed optimism about the trial outcomes, highlighting that these results offer a clearer understanding of temtokibart’s mode of action, potentially addressing unmet needs in other diseases where the IL-22 pathway plays a significant role. LEO Pharma is also exploring the application of temtokibart for treating inflammation-induced anemia.

LEO Pharma and argenx, a global immunology company, established a strategic partnership in 2015 to create innovative antibody-based treatments for chronic inflammation underlying various skin conditions. Under this partnership, temtokibart was jointly developed, and LEO Pharma obtained the license in 2022, assuming the responsibility for its development and commercialization.

Atopic dermatitis (AD) is a chronic inflammatory skin condition marked by intense itching and eczematous lesions. It results from a combination of skin barrier dysfunction and immune dysregulation, leading to persistent inflammation. Type 2 cytokines, such as IL-13, play a crucial role in the disease's pathophysiology, with excessive IL-22 production also contributing to the condition.

LEO Pharma, founded in 1908 and majority-owned by the LEO Foundation, is a global company dedicated to improving the standard of care for individuals with skin conditions. Headquartered in Denmark and with a global team of 4,200 people, LEO Pharma serves millions of patients worldwide, generating net sales of DKK 11.4 billion in 2023.