Background/Purpose: GP2017 is a proposed adalimumab biosimilar that has been shown to be similar to reference adalimumab at an analytical and preclinical level. The aim of this study was to determine the pharmacokinetics (PK), immunogenicity and safety of GP2017, EU-authorized adalimumab (EU-adalimumab) and US-licensed adalimumab (US-adalimumab) in healthy volunteers. As part of the global development program for GP2017, a further aim was to establish PK bridging data between EU- and US-adalimumab.

Methods: This was a randomized, double-blind, three-arm parallel study in healthy male volunteers aged 18 to 55 years, with a body mass index of 18.5 to 29 kg/m². Subjects were randomized to receive a single 40 mg/0.8 mL subcutaneous injection of either GP2017, EU- or US-adalimumab, with follow-up until Day 72.  The primary objective was to demonstrate PK bioequivalence between GP2017 and EU-adalimumab, and between EU-adalimumab and US-adalimumab, by describing maximum observed serum concentration (C_max) and total area under the curve (AUC_0-inf). Secondary objectives included the assessment of AUC_0-360h and AUC_0-last, the comparison of PK parameters between GP2017 and US-adalimumab, and the evaluation of safety, tolerability and immunogenicity of all three products.

Results: A total of 318 subjects were randomized to GP2017 (n=107), EU-adalimumab (n=106) and US-adalimumab (n=105). Baseline characteristics, including body weight, were well balanced across treatment arms. For C_max and AUC_0-inf the 90% confidence interval (CI) for the ratio of geometric means was contained within prespecified bioequivalence limits of 0.8 to 1.25 for the primary analysis of GP2017 and EU-adalimumab, and EU- and US-adalimumab (Table). For the analysis of secondary objectives, 90% CI were contained within 0.8 to 1.25 for all pairwise comparisons of C_max, AUC_0-inf, AUC_0-360h and AUC_0-last (Table). The incidence of drug-related, treatment-emergent adverse events (TEAEs) was similar across the GP2017/EU-adalimumab/US-adalimumab treatment groups (57.9%/61.3%/58.1%) and all were mild or moderate in severity. Infections/infestations were the most common TEAEs. Injection site reactions were infrequent and mild. Overall, antidrug antibodies  were detected in 57.9%/69.8%/69.5% of subjects in the GP2017/EU-adalimumab/US-adalimumab groups up to Day 72, which were neutralizing in 54.2%/ 64.2%/62.9% of subjects, respectively.

Conclusion: The results show that GP2017 is bioequivalent to EU- and US-adalimumab and EU-adalimumab is bioequivalent to US-adalimumab. There were no clinically relevant differences in safety, tolerability and immunogenicity among the three treatment arms in healthy subjects.