AB0380 Results from a randomized, single-blind, single-dose, parallel-group study in healthy subjects demonstrating pharmacokinetic similarity between abp 710 and infliximab

Background ABP 710 is being developed as a biosimilar with the same amino acid sequence as infliximab, an anti-tumor necrosis factor therapy. Analytical and functional comparisons between ABP 710 and infliximab have been conducted and completed. Objectives This report describes the results of analyses comparing the pharmacokinetics (PK), safety, and immunogenicity of ABP 710 and infliximab sourced from the European Union (EU). Methods This was a single-blind, single-dose, parallel-group study among healthy adults, 18 to 45 years of age and with a body mass index of 18 to 30 kg/m2. Subjects were randomized to receive a 5 mg/kg intravenous infusion of either ABP 710 or infliximab. The primary objective of this analysis was demonstration of PK similarity of ABP 710 to infliximab based on area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf; primary endpoint). PK equivalence was deemed achieved if the geometric mean (GM) ratio and its 90% confidence interval (CI) for AUCinf was within the range of 0.80 and 1.25. Secondary endpoints included maximum observed serum concentration (Cmax), area under the serum concentration-time curve from time 0 to last quantifiable concentration (AUClast), safety, and immunogenicity. Results Pharmacokinetics: A total of 49 subjects received ABP 710 and 49 subjects received infliximab. Following a single dose, the adjusted least square (LS) GM of AUCinf, AUClast, and Cmax for ABP 710 was 33559 μg·h/mL, 31789 μg·h/mL, and 123 μg/mL, respectively. The adjusted LS GM of AUCinf, AUClast, and Cmax for infliximab was 33706 μg·h/mL, 31847 μg·h/mL, and121 μg/mL, respectively. Ratios of adjusted LS GMs (90% CIs) between ABP 710 and infliximab for AUCinf, AUClast, and Cmax were 0.996 (0.904, 1.096), 0.998 (0.918, 1.086), and 1.021 (0.962, 1.083), respectively. Safety: There was one subject in the infliximab group who developed polyarthritis that resolved with treatment and the subject completed the study. There were no deaths, other serious adverse events, or treatment-emergent adverse events (TEAEs) leading to discontinuation from the study. The incidence of TEAEs was similar in the two treatment groups (ABP 710: 83.7%; infliximab: 83.7%); the majority of TEAEs were mild or moderate. The most frequently reported TEAEs were somnolence, headache, nasopharyngitis, upper respiratory tract infection, nausea, and lethargy. Immunogenicity: All subjects tested negative for antidrug antibodies (ADAs) prior to dosing. At the end of study (Day 57), 40% of subjects in the ABP 710 group and 27% in the infliximab group were positive for binding ADAs, and 13% of subjects in the ABP 710 group and 19% in the infliximab group were positive for neutralizing ADAs. Conclusions Results of this phase 1 study demonstrate PK similarity between ABP 710 and infliximab sourced from the EU among healthy subjects. The safety and immunogenicity profile were comparable between the treatment groups. Disclosure of Interest E. Krishnan Shareholder of: Amgen Inc., Employee of: Amgen Inc., V. Chow Shareholder of: Amgen Inc., Employee of: Amgen Inc., N. Zhang Shareholder of: Amgen Inc., Employee of: Amgen Inc., A. Kaliyaperumal Shareholder of: Amgen Inc., Employee of: Amgen Inc., P. Kaur Shareholder of: Amgen Inc., Employee of: Amgen Inc.