LEO Pharma announced promising results from a phase 2a mechanism of action trial comparing its investigational IL-22 inhibitor temtokibart to dupilumab in patients with moderate-to-severe atopic dermatitis. The late-breaking data, presented at the European Academy of Dermatology and Venereology (EADV) 2024 annual meeting, demonstrated that temtokibart achieved comparable clinical efficacy to the established therapy while showing superior improvements in skin barrier function.
Trial Design and Methodology
The randomized, double-blind, active comparator-controlled trial enrolled adult patients with moderate-to-severe atopic dermatitis at a single site over 16 weeks. Participants were randomized in a 2:1 ratio to receive either temtokibart 450 mg or dupilumab 300 mg administered every two weeks. The primary endpoint focused on changes in gene expression associated with atopic dermatitis in lesional skin biopsies from baseline to week 4, while secondary endpoints included treatment-emergent adverse events through week 16.
Superior Skin Barrier Improvements
Temtokibart demonstrated faster and more pronounced improvements in skin hydration compared to dupilumab. The IL-22 inhibitor achieved significant improvements in natural moisturizing factors, specifically 2-pyrrolidone-5-carboxylic acid and urocanic acid, at just one week from baseline (P <0.0001). These findings suggest temtokibart's unique mechanism of targeting the IL-22RA1 receptor provides direct benefits to skin barrier function without requiring immune cell targeting.
Clinical improvements in Eczema Area and Severity Index (EASI) scores and itch Numeric Rating Scale measurements were comparable between both treatments by week 16, indicating similar overall disease control despite different mechanisms of action.
Novel Therapeutic Pathway
"The results of this trial provide new insights into the pathophysiology of atopic dermatitis and give us a unique understanding of the mode of action of temtokibart," said principal investigator Christine Bangert, MD, head of the Allergology Task Force of the Austrian Society of Dermatology and Venereology. "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."
The findings challenge the current understanding of atopic dermatitis treatment, which has primarily focused on Type 2 inflammatory pathways. Temtokibart's ability to improve skin barrier dysfunction through IL-22 inhibition represents a complementary approach that could address unmet medical needs in dermatology.
Development Pipeline and Future Prospects
LEO Pharma has completed recruitment for an ongoing phase 2b dose-finding trial evaluating different temtokibart doses in adult patients with moderate-to-severe atopic dermatitis. The study's primary endpoint measures percent change in EASI score from baseline to week 16, with results anticipated in Q1 2025.
"We are encouraged by the results of this atopic dermatitis trial exploring how targeting the disease from different angles with different mechanisms of action impacts disease markers," stated Kreesten Meldgaard Madsen, chief development officer at LEO Pharma. The company is also investigating temtokibart for inflammation-induced anemia, highlighting the broader therapeutic potential of IL-22 pathway modulation.
Additional EADV Developments
At the same conference, LEO Pharma presented late-breaking data from the DELTA FORCE trial comparing delgocitinib cream (Anzupgo) to oral alitretinoin capsules for chronic hand eczema. The topical treatment demonstrated significantly greater decreases in Hand Eczema Severity Index scores from baseline to week 12 (P <0.001), further expanding the company's dermatology portfolio.
The temtokibart results represent a significant advancement in understanding atopic dermatitis pathophysiology and offer potential for patients who may benefit from alternative therapeutic mechanisms beyond current Type 2 inflammation-targeting treatments.
