Pharmacokinetics and safety of candidate tocilizumab biosimilar CT-P47 versus reference tocilizumab: a randomized, double-blind, single-dose phase I study

ABSTRACT Background CT-P47 is a candidate tocilizumab biosimilar. This study assessed the pharmacokinetic (PK) equivalence of CT-P47 and European Union-approved reference tocilizumab (EU-tocilizumab) in healthy Asian adults. Research design and methods This double-blind, multicenter, parallel-group trial randomized healthy adults (1:1) to receive a single (162 mg/0.9 mL) subcutaneous dose of CT-P47 or EU-tocilizumab. The primary endpoint (Part 2) was PK equivalence by area under the concentration – time curve (AUC) from time zero to last quantifiable concentration (AUC0–last), AUC from time zero to infinity (AUC0–inf), and maximum serum concentration (Cmax). PK equivalence was concluded if 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were within the 80–125% equivalence margin. Additional PK endpoints, immunogenicity, and safety were evaluated. Results In Part 2, 289 participants were randomized (146 CT-P47; 143 EU-tocilizumab); 284 received study drug. AUC0–last, AUC0–inf, and Cmax were equivalent between CT-P47 and EU-tocilizumab: 90% CIs for the ratios of gLSMs were within the 80–125% equivalence margin. Secondary PK endpoints, immunogenicity, and safety were comparable between groups. Conclusions CT-P47 demonstrated PK equivalence with EU-tocilizumab and was well tolerated, following a single dose in healthy adults. Clinical trial registration www.clinicaltrials. gov identifier is NCT05188378. Plain Language Summary Tocilizumab is a biologic medicine used to treat inflammatory diseases including rheumatoid arthritis. Biosimilars are drugs that are highly similar to an already approved, ‘reference’ biologic medicine. This means that they do not have any differences from the reference product in factors including structure, biologic function, efficacy, and safety, that might affect how well they work in patients. Biosimilars are often available at a lower cost than reference drugs, so their use can provide patients with better access to expensive treatments. There are no approved biosimilars of tocilizumab so far: CT-P47 is currently in development as a potential tocilizumab biosimilar. In the main part of this study, 289 healthy Asian volunteers were randomly allocated to receive a single injection of either CT-P47 or the reference drug, European Union-approved tocilizumab (EU-tocilizumab). The main aim of the study was to find out whether CT-P47 and EU-tocilizumab were equivalent in terms of pharmacokinetics (drug absorption, distribution, metabolism, and excretion by the body). This is part of a standard process required by regulatory authorities to ensure that biosimilars work as well as their reference drugs. Analysis of blood samples taken over 43 days showed that the pharmacokinetic profiles of CT-P47 and EU-tocilizumab were equivalent, after the volunteers received a single dose of either drug. Safety and immunogenicity (immune responses made to the drug) were also comparable between CT-P47 and EU-tocilizumab. While only healthy Asian adults were included, further research comparing CT-P47 with reference tocilizumab will help to ensure that the findings from the study can be applied to broader populations.