Comparative assessment of pharmacokinetic parameters between HS016, an adalimumab biosimilar, and adalimumab (Humira (R)) in healthy subjects and ankylosing spondylitis patients: Population pharmacokinetic modeling

Background. The HS016 is an adalimumab biosimilar related to the immunoglobulin G1 (IgG1) antibody, with a similar amino acid sequence. Objectives. To quantify the differences in the pharmacokinetic (PK) parameters of HS016 and adalimumab in healthy individuals and patients with ankylosing spondylitis (AS). Materials and methods. The PK data for HS016 and adalimumab were obtained in a randomized, doubleblind, phase 1 clinical study in Chinese healthy subjects after a single-dose subcutaneous administration (136 healthy subjects), and in a randomized, double-blind, phase 3 trial of AS patients who received subcutaneous injection of HS016 or adalimumab once every 2 weeks for 24 weeks (366 AS patients). Results. The time course of HS016 and adalimumab was characterized by a one-compartment model with firstorder absorption and elimination kinetics. Age, body weight, creatinine clearance (CLcr) and anti-drug antibody were covariates for the apparent clearance (CL/F); body weight and subject type were significant covariates for the apparent volume of distribution (V/F). The V/F and CL/F were estimated at 11.3 L and 0.0102 L/h. The ratios of the geometric least square (LS) means (HS016 compared to the adalimumab treatment group after multiple doses) in healthy subjects were 97.14 (87.70, 107.59) for the concentration-time curve from time zero to the last measurable concentration (AUC(0-t)) and 99.14 (90.03, 109.16) for the maximum serum drug concentration within a steady-state dosing interval (C-max,C-ss); the ratios (90% confidence interval (90% CI)) in AS patients were 97.03 [84.10; 111.96] for the AUC within the steady-state dose intervals (AUC(0-tau)) and 99.62 [88.09; 112.68] for C-max,C- ss. Conclusions. The systemic exposure of HS016 was similar to that of adalimumab in healthy subjects and AS patients, demonstrating PK similarity.