Population Pharmacokinetic Analysis of Vixarelimab in Healthy Volunteers and Patients With Chronic Pruritic Conditions.

Vixarelimab is a first-in-class fully human monoclonal antibody targeting oncostatin M (OSM) receptor beta (OSMRβ). It has been evaluated in Phase 1 and 2 studies in healthy volunteers and patients with chronic pruritic conditions and demonstrated anti-pruritic efficacy in a Phase 2 study in prurigo nodularis, but detailed pharmacokinetic analysis has not been previously reported. In this study, a population pharmacokinetic analysis was performed to characterize the pharmacokinetics of vixarelimab and identify covariates affecting exposure. The analysis dataset contained 4032 measurements from 274 participants from three Phase 1 and 2 studies. A two-compartment target-mediated drug disposition (TMDD) model with a quasi-steady-state (QSS) approximation satisfactorily described the observed concentration-time data across studies and various dose levels. The model estimated linear clearance (CL), central volume (Vc), and peripheral volume (Vp) at 0.00649 L/h, 3.04 L, and 1.74 L, respectively, in line with values for a typical monoclonal antibody. Subcutaneous bioavailability and the absorption rate constant were estimated to be 56.6% and 0.0126 h-1, respectively. Body weight was identified as the only statistically significant covariate, positively correlating with CL, Vc, and Vp. Model-based simulations showed that the clinical impact of body weight on vixarelimab exposure was minor, suggesting that dose adjustment based on weight is not warranted. The developed model provides a thorough understanding of vixarelimab pharmacokinetics and the impact of covariates on exposure to support future clinical development.