Amlitelimab reduces atopic dermatitis-related gene expression elevated in lesional skin: An analysis of the phase 2b STREAM-AD study

Summary: Abstract Body: Amlitelimab (SAR445229) is a fully human, nondepleting, anti-OX40 ligand monoclonal antibody. In the STREAM-AD phase 2b trial (NCT05131477), amlitelimab, given subcutaneously every 4wks, demonstrated clinically meaningful improvements in patients with atopic dermatitis (AD) and reduced AD-related plasma and cutaneous biomarkers over 24wks compared with placebo-treated patients. This analysis evaluates the effect of amlitelimab on AD-related genes. Differential gene expression analysis was performed between baseline lesional and nonlesional skin biopsies (amlitelimab, n=43; placebo, n=12) and between baseline and on-treatment lesional skin biopsies (amlitelimab, n=27; placebo; n=7) with a specific focus on Th1, Th2, and Th17/22 pathway-associated genes. Normalization of gene expression levels at Wk16 in treated lesional skin toward baseline nonlesional skin was visualized using percent recovery [% recovery= Log2FCW16vsW0-LS*100/(-Log2FCLSvNL-Baseline)]. Amlitelimab led to downregulation of Th1 (eg, CXCL9 and CXCL10; P<0.05), Th2 (eg, CCL13 and CCL18; P<0.05), and Th17/22 (eg, S100A8 and S100A9; P<0.05) pathway-associated genes in lesional skin at Wk16 compared with baseline, and a greater % recovery toward nonlesional gene expression levels than placebo. The observed normalization of AD-related genes in lesional skin after 16wks of amlitelimab treatment supports the clinical improvements seen in AD lesions in STREAM-AD. Emma Guttman-Yassky¹, Kenji Kabashima², Killian Eyerich³, Charles Lynde⁴, Jean-David Bouaziz⁵, Frank Auge⁶, Chris Hoefler⁷, Shaima Belhechmi⁸, Natalie Rynkiewicz⁹ 1. Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2. Kyoto University, Kyoto, Japan. 3. University of Freiburg, Freiburg, Germany. 4. Probity Medical Research and University of Toronto, Toronto, NU, Canada. 5. Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris and Paris Cité University, Medicine Faculty of Paris Cité, Paris, France, Paris, France. 6. Formerly Sanofi, Chilly-Mazarin, Please Select, France. 7. Sanofi, Cambridge, MA, United States. 8. Sanofi, Paris, Please Select, France. 9. Sanofi, Cambridge, Please Select, United Kingdom. Clinical Research: Interventional Research