LEO Pharma A/S announced positive topline results from its Phase 2b clinical trial evaluating temtokibart (LEO 138559), an investigational IL-22RA1 antagonist, for the treatment of adults with moderate-to-severe atopic dermatitis (AD).
The randomized, double-blind, placebo-controlled, multi-site trial assessed the efficacy and safety of different doses of subcutaneously administered temtokibart in adult patients with moderate-to-severe AD. The study met its primary endpoint, demonstrating significant percentage change in Eczema Area and Severity Index (EASI) from baseline to Week 16 for the three highest doses tested.
Safety data indicated that temtokibart was generally well-tolerated across all dosing groups. The majority of adverse events were non-serious, mild or moderate in severity, and not considered treatment-related. Importantly, researchers observed no dose-dependent safety concerns.
"Atopic dermatitis is a complex immunological condition, and patients living with this debilitating disease still face unmet needs," said Dr. Jacob Pontoppidan Thyssen, Chief Scientific Officer & Executive Vice President, Science, Search & Innovation at LEO Pharma. "We are encouraged by the results of this Phase 2b trial, which has explored how to target the disease from a different angle with a different mechanism of action, compared to what is commonly used today to treat AD."
Novel Mechanism of Action
Temtokibart represents a novel approach to treating atopic dermatitis. As a monoclonal antibody, it specifically targets the IL-22RA1 receptor subunit, thereby inhibiting the effects of the interleukin-22 (IL-22) cytokine, which is known to be elevated in patients with atopic dermatitis. The drug also inhibits IL-20 and IL-24 signaling but does not bind to the IL-22 cytokine itself.
This mechanism differs from many current AD treatments that target other inflammatory pathways. Excessive IL-22 production has been identified as a contributor to the pathogenesis of atopic dermatitis, making it a promising therapeutic target.
Collaborative Development
The development of temtokibart stems from a strategic alliance formed in 2015 between LEO Pharma and argenx, a global immunology company. The companies jointly developed the drug under this research agreement, with LEO Pharma subsequently obtaining the exclusive license to develop and commercialize temtokibart.
LEO Pharma is currently collecting and evaluating the complete data set from the Phase 2b trial. Detailed results are planned for submission to scientific conferences and publications at a later date.
Trial Design and Endpoints
The Phase 2b trial (NCT05923099) randomized patients to receive one of four doses of temtokibart or placebo. The primary endpoint was percent change in EASI from baseline to Week 16, while the key secondary endpoint was the number of treatment-emergent adverse events from baseline to Week 16 per subject.
Understanding Atopic Dermatitis
Atopic dermatitis affects millions worldwide and is characterized by intense itching and eczematous lesions. The chronic inflammatory skin condition results from skin barrier dysfunction and immune dysregulation, leading to persistent inflammation.
Current understanding of AD pathophysiology highlights the role of Type 2 cytokines, including IL-13, in driving the disease. However, research has also identified excessive IL-22 production as a significant contributor to AD pathogenesis, providing the rationale for temtokibart's development.
Addressing Unmet Needs
Despite advances in AD treatment in recent years, many patients continue to experience inadequate disease control or intolerance to available therapies. The positive results from temtokibart's Phase 2b trial suggest potential for a new treatment option with a different mechanism of action.
Dr. Thyssen noted that these results "further add to the understanding of the mode of action of temtokibart and its potential abilities to address unmet needs in diseases where the IL-22 pathway is known to play a key role – in medical dermatology and beyond."
The successful development of temtokibart could provide dermatologists and patients with an additional therapeutic option for managing moderate-to-severe atopic dermatitis, potentially benefiting those who have not responded adequately to existing treatments.
About LEO Pharma
LEO Pharma is a global leader in medical dermatology with a century of experience developing breakthrough medicines. The company serves approximately 100 million patients in over 70 countries annually. Headquartered in Denmark, LEO Pharma employs around 4,000 people worldwide and is co-owned by the LEO Foundation and Nordic Capital.
