Background/Purpose: ABP 501 has been developed as a biosimilar for Humira® (adalimumab), a fully human monoclonal antibody targeting tumor necrosis factor alpha (TNFα). ABP 501 is the first adalimumab biosimilar approved in the United States (AMJEVITA™) and European Union (AMGEVITA®) as a 50 mg/mL formulation for treating certain immune-mediated inflammatory diseases. An ABP 501 100 mg/mL formulation is being developed as a high-concentration formulation and requires half the injection volume to deliver the same subcutaneous (SC) dose. This study evaluates the similarity between single-dose pharmacokinetics (PK), safety, and immunogenicity of the low-concentration (ABP 501-LCF) and high-concentration (ABP 501-HCF) formulations of ABP 501 in healthy adult subjects.

Methods: In this randomized, single-blind, single-dose, 2-arm, parallel-group study in healthy adults, approximately 350 subjects were planned for dosing. Eligible subjects were randomized in a 1:1 ratio to receive a single 40 mg SC injection of either ABP 501-HCF (n = 175) or ABP 501-LCF (n = 175). The primary objective was to determine PK similarity of ABP 501-HCF with ABP 501-LCF, as assessed by area under the concentration time curve from time 0 extrapolated to infinity (AUC_inf) and maximum observed concentration (C_max). Pre-specified similarity criterion for the primary PK analysis was the standard 90% confidence interval (CI) for the ratio of least square (LS) geometric means (GM) to be within 0.80 to 1.25. Secondary endpoints included other PK parameters, safety, tolerability, and immunogenicity.

Results: A total of 370 of 372 randomized subjects received study drug (ABP 501-HCF, n = 183 of 185; ABP 501-LCF, n = 187 of 187). Demographic and baseline characteristics were comparable between the two treatment groups. Ratios of LS GM (90% CIs) between ABP 501-HCF and ABP 501-LCF for AUC_inf and C_max were 1.04 (0.9634, 1.1297) and 1.06 (0.9960, 1.138); the 90% CIs (for the ratio of LS GM between ABP 501-HCF and ABP 501-LCF for AUC_inf and C_max) were fully contained within the prespecified PK similarity margin (0.8 – 1.25) (Table 1). Both the high- and low-concentration formulations were well tolerated; the frequency, type, and severity of adverse events (AEs) were comparable between ABP 501-HCF and ABP 501-LCF and were consistent with the safety profile of adalimumab (Table 2). Headache was the most commonly reported AE in both treatment groups (ABP 501-HCF, n = 8; ABP 501-LCF, n = 9). Subjects in both groups tested positive for pre-existing binding anti-drug antibodies (ADAs) and neutralizing ADAs at baseline; 182 subjects in the ABP 501-HCF group and 185 in the ABP 501-LCF group had post-baseline results through end of study (Table 3). In the ABP 501-HCF group, 165 (90.7%) subjects developed binding ADAs and 31 (17%) developed neutralizing ADAs. In the ABP 501-LCF group, 171 (92.4%) subjects developed binding ADAs and 29 (15.7%) developed neutralizing ADAs.

Conclusion: Results of this study demonstrate PK similarity between ABP 501-HCF (100 mg/mL) and ABP 501-LCF (50 mg/mL) following a single SC injection in healthy adult subjects. Immunogenicity and safety of ABP 501-HCF and ABP 501-LCF were also found to be similar.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetic-and-safety-similarity-of-high-and-low-concentration-formulations-of-adalimumab-biosimilar-abp-501/