Population pharmacokinetics of ozoralizumab in patients with rheumatoid arthritis.

Ozoralizumab is a bispecific NANOBODY® compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin (HSA). Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its HSA-binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis (RA) in phase II/III and phase III trials to assess the effects of potential PK covariates. The ozoralizumab PK after subcutaneous administration was described using a one-compartment model with first-order absorption and first-order elimination processes. A proportional error model was used for inter- and intra-individual variabilities, with covariance set between inter-individual variabilities of the apparent clearance (CL/F) and apparent distribution volume (Vd /F). Body weight, sex, anti-drug antibody status, estimated glomerular filtration rate, and concomitant methotrexate use were identified as covariates for CL/F, while body weight and sex were covariates for Vd /F in the final model. Body weight had the greatest effect on the PK of ozoralizumab, while the other covariates had minor effects. When administered at 30 mg every 4 weeks, the predicted steady-state plasma trough concentration in a patient weighing 83.2 kg exceeded the trough concentration required to maintain efficacy of ozoralizumab, and the estimated exposure in a patient weighing 42.5 kg did not exceed the mean exposure at 80 mg, a well-tolerated dose, throughout 52 weeks. We developed a population PK model that adequately described the ozoralizumab PK in Japanese patients with RA, and none of the evaluated covariates showed clinically relevant effects on the PK of ozoralizumab. This article is protected by copyright. All rights reserved.