Temtokibart Proves Comparable to Dupilumab for Atopic Dermatitis in Phase 2a Trial

Christine Bangert, MD
Credit: Medical University of Vienna

Late-breaking data from the European Academy of Dermatology and Venereology (EADV) 2024 shed new light on the potential benefits of the IL-22 inhibitor temtokibart in management of moderate to severe atopic dermatitis.

A 16-week phase 2a mechanism of action trial evaluating the use of temtokibart 450 mg against dupilumab (Dupixent) 300 mg, results indicated use of temtokibart provided similar reductions in clinical disease activity as dupilumab, which Leo Pharma suggests indicates the identification of a new treatment with potential benefit for patients with moderate to severe atopic dermatitis.^1,2

“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 and head of the atopic eczema outpatient clinic of the Medical University of Vienna.² “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 phase 2 temtokibart trial was a randomized, double-blind, active comparator-controlled, 16-week trial conducted at a single site to evaluate the effect of temtokibart on the molecular signature and safety in adults with moderate-to-severe atopic dermatitis. Per trial protocol, patients were randomized in a 2:1 ratio to temtokibart 450 mg every 2 weeks or dupilumab 300 mg every 2 weeks for a 16-week treatment period.^1,2

The trial’s primary endpoint of interest was the change in gene expression typically associated with atopic dermatitis in lesional skin biopsies from baseline to week 4. The trial also included a secondary outcome of interest, which was defined as the number of treatment-emergent adverse events from baseline to week 16 per subject.^1,2

According to data from the phase 2a trial, temtokibart achieved improvements in skin hydration faster and to a greater extent than dupilumab. Results from the study demonstrated use of temtokibart was associated with significant improvements in natural moisturizing 2-pyrrolidone-5-carboxylic acid and urocanic acid at 1 week from baseline (P <.0001). Further analysis of data suggested clinical improvements in Eczema Area and Severity Index and itch Numeric Rating Scale from baseline to Week 16 were comparable for temtokibart and dupilumab.^1,2

In their release, Leo Pharma highlighted an ongoing phase 2b dose-finding trial examining different doses of temtokibart in adult patients with moderate to severe atopic dermatitis. The primary endpoint of interest in this trial is the percent change in EASI score from baseline to Week 16. According to the release, this trial has finalized recruitment and results are expected in Q1 2025.²

“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,” said Kreesten Meldgaard Madsen, chief development officer at LEO Pharma.² “These results further clarify the mode of action of temtokibart, giving reasons to believe temtokibart could also address unmet needs in other diseases where the IL-22 pathway is known to play a key role. LEO Pharma is currently exploring temtokibart for inflammation induced anemia.”

At EADV 2024, Leo Pharma also announced late-breaking data from delgocitinib cream (Anzupgo) in the management of chronic hand eczema. Named the DELTA FORCE trial, the study compared delgocitinib head-to-head against oral alitretinoin capsules and concluded delgocitinib was associated with significantly greater decreases in Hand Eczema Severity Index score from baseline to week 12 (P <.001).³

References:

1. Bangert C, Berdyshev E, Alkon N, et al. Targeting IL-22RA1 with temtokibart in patients with moderate to severe atopic dermatitis induces fast clinical and molecular responses, distinct from dupilumab. Presented at: European Academy of Dermatology and Venereology (EADV) 2024. September 25-28, 2024.
2. Leo Pharma. Leo Pharma presents late-breaking results from the phase 2A mechanism of action trial of Temtokibart and dupilumab in moderate-to-severe atopic dermatitis at the 2024 EADV annual meeting. Leo Pharma. September 26, 2024. Accessed September 26, 2024. https://www.leo-pharma.com/media-center/news/2024-leo-pharma-presents-late-breaking-results.
3. Leo Pharma. Leo Pharma Presents late-breaking Anzupgo® (delgocitinib) cream presentation at EADV 2024 highlighting results of head-to-head Delta Force trial in chronic hand eczema (CHE). Leo Pharma. September 24, 2024. Accessed September 26, 2024. https://www.leo-pharma.com/media-center/news/2024-leo-pharma-presents-late-breaking-anzupgo-cream-presentation-at-eadv-2024.