Skin transcriptome modulation in Japanese patients with atopic dermatitis treated with rocatinlimab, an anti-OX40 receptor antibody

Summary: Abstract Body: Rocatinlimab (AMG 451/KHK4083) is an investigational therapy that inhibits and reduces pathogenic T cells by targeting the OX40 receptor. Rocatinlimab demonstrated efficacy and was generally well-tolerated in moderate-to-severe atopic dermatitis (msAD) in a global placebo (PBO)-controlled, Phase 2b study (NCT03703102). This post hoc analysis in Japanese patients (n=147) explores efficacy and biomarker responses. Patients were randomized to receive subcutaneous rocatinlimab 150 mg every 4 weeks (wks) (Q4W), 600 mg Q4W, 300 mg every 2 wks (Q2W), 600 mg Q2W, or PBO. A double-blind period (to Wk 18) was followed by an active-treatment extension (Wks 18–36; PBO switched to 600 mg Q2W) and an off-treatment follow-up (Wks 36–56). Eczema Area and Severity Index (EASI) and pruritus numerical rating scale (pNRS) scores were evaluated from baseline (BL), and gene expression in non-lesional and lesional skin biopsies were assessed by microarray. Like the global population, greater improvement in EASI score from BL vs PBO was reported as early as Wk 2 with responses maintained through Wk 36 and off-treatment to Wk 56 (Wk 36 LS mean % change in EASI score from BL: -77.81 to -90.15), consistent with improved pNRS scores. Skin transcriptome analysis demonstrated improvement of a meta-analysis derived AD transcriptome at Wks 8, 16, 36, and 52 in lesional and non-lesional skin, consistent with clinical outcomes. Pronounced gene signatures modulated vs BL were related to Th1, Th2, Th17, and Th22 cells, and markers of tissue resident memory T cells and epidermal barrier function (Wk 52, all p<0.05). Rocatinlimab induced durable efficacy with acceptable safety and meaningful biomarker responses, demonstrating potential T-cell rebalancing in Japanese patients with msAD. Kenji Kabashima¹, Masato Komai², Ehsanollah Esfandiari³, Hirotaka Mano², Tetsuro Tomiyama², Daisuke Takaichi², Munetake Shimabe⁴, Emma Guttman-Yassky⁵ 1. Department of Dermatology, Kyoto University, Kyoto, Japan. 2. Kyowa Kirin, Tokyo, Japan. 3. Kyowa Kirin International, London, United Kingdom. 4. Kyowa Kirin, Princeton, NJ, United States. 5. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Clinical Research: Interventional Research