Population Pharmacokinetics of Xeligekimab: An Anti‐IL‐17A Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis

Abstract Xeligekimab, a recombinant fully human IgG4 monoclonal antibody, has been strategically developed to target IL‐17A and is presently in the developmental phase for treating moderate to severe plaque psoriasis. This study aims to investigate the pharmacokinetic profile of Xeligekimab, utilizing data derived from clinical trials specifically conducted in Chinese patients. The study conducted a population pharmacokinetic (PopPK) analysis involving 614 patients with plaque psoriasis. Examined covariates encompassed demographics, baseline laboratory tests, anti‐drug antibodies (ADA), injection site, and disease‐related baseline characteristics. Model evaluation utilized goodness‐of‐fit, prediction‐corrected visual prediction check, and bootstrap methods. The clinical significance of covariates statistically associated with Xeligekimab was assessed through simulation analysis. The PopPK model of Xeligekimab demonstrated characteristics of a two‐compartment model with first‐order absorption and linear elimination. Inter‐individual variability (IIV) was estimated for clearance and volume of distribution. For a typical plaque psoriasis patient, the estimated values for absorption rate constant (Ka), apparent clearance (CL/F), central compartment volume (V c /F), peripheral compartment volume (V p /F), and inter‐compartmental clearance (Q/F) was 0.225 per day, 2.223 L/day, 4.02 L, 4.13 L, and 1.11 L/day, respectively. The estimated IIV for CL/F and V c /F was 25.8% and 49.8%, respectively. The elimination half‐life (t 1/2 ) was approximately 28.5 days. CL/F was significantly influenced by factors such as body weight, age, gender, and baseline total protein. V c /F was significantly influenced by body weight, age, gender, and baseline albumin. However, the clinical relevance of these covariate effects on exposure parameters was determined to be limited.