AUTHOR=Cao Guoying , Wang Jingjing , He Jinjie , Hu Yingying , Yang Haijing , Que Linling , Gu Xianghong , Yu Jicheng , Wu Xiaojie , Wu Jufang , Fang Wei , He Qing , Zhang Jing 

TITLE=LZM008, a proposed tocilizumab biosimilar: Pharmacokinetics, safety, and immunogenicity profiles compared with ACTEMRA® in Chinese healthy male subjects

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1111893

DOI=10.3389/fphar.2023.1111893

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> This study aimed to investigate the pharmacokinetics, safety, and immunogenicity of recombinant humanized anti-human IL-6R monoclonal antibody injection, LZM008, and evaluate the pharmacokinetic similarity between LZM008 and tocilizumab (ACTEMRA<sup>®</sup>) in Chinese healthy male subjects.</p><p><bold>Research design and methods:</bold> In this randomized, double-blinded, paralleled, two-center Phase I clinical trial, 96 subjects were randomized with a 1:1 ratio to receive 4 mg/kg intravenous dose of LZM008 or ACTEMRA<sup>®</sup> and evaluated for 28 days. The pharmacokinetic bioequivalence was assessed by the maximum serum concentration (C<sub>max</sub>), the area under the serum concentration–time curve (AUC) from time 0 to the last detectable drug concentration (AUC<sub>0-t</sub>), and AUC<sub>0-∞</sub>. The statistical analysis was conducted using SAS Enterprise Guide statistical software. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Anti-drug antibodies (ADAs) were measured by a bridged electrochemiluminescence immunoassay.</p><p><bold>Results:</bold> LZM008 (N = 49) and ACTEMRA<sup>®</sup> (N = 47) groups showed similar pharmacokinetic properties. After a single intravenous infusion of 4 mg/kg LZM008, the C<sub>max</sub> and AUC<sub>0-∞</sub> values of LZM008 reached 87.99 μg/mL and 11,526.70 h*μg/mL, respectively, with T<sub>max</sub> 1.98 h, and the half-life (t<sub>1/2</sub>) was 83.45 h. The 90% confidence intervals of ratios for C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> were within the range of 80.00%–125.00%. After infusion, one (2.0%) subject in the LZM008 group and three (6.4%) subjects in the ACTEMRA<sup>®</sup> group showed positive ADA test results. The incidence of treatment emergent adverse events (TEAEs) was comparable in LZM008 and ACTEMRA<sup>®</sup> groups (98.0% <italic>versus</italic> 100%), with the decrease in blood fibrinogen and neutrophil counts being the most common TEAEs.</p><p><bold>Conclusion:</bold> The pharmacokinetic characteristics and immunogenicity exhibited by LZM008 were similar to those of the reference product, ACTEMRA<sup>®</sup>. The safety profiles of LZM008 were similar in the two groups with mild–moderate adverse effects.</p><p><bold>Trial Registration:</bold> The trial is registered at <ext-link ext-link-type="uri" xlink:href="http://www.chinadrugtrials.org.cn" xmlns:xlink="http://www.w3.org/1999/xlink">www.chinadrugtrials.org.cn</ext-link> (CTR20190889).</p>