met the pre-specified acceptance criteria for the relevant pharmacokinetic/pharmacodynamic parameter endpoints. A summary of the results of these studies are presented in the table below (Table 1). Table 1: Summary of phase I pharmacokinetic studies of potential biosimilar medicines PK Outcomes (and Biosimilar Reference Immunogenicity Study Design PD where Reference Candidate Product Population Outcomes reported) Bevacizumab (Amgen) US and EU Randomized, Healthy male 90% CI for the No anti-drug [1] Avastin single-blind, volunteers ratio of treatment antibodies detected 1mg/kg three-arm, (n= 202) means for at baseline or at end parallel- group of study study (1:1:1) from time zero extrapolated to infinite time (AUCinf) and maximal plasma concentration (Cmax) were within the prespecified limits of 80- 125% for the comparisons of ABP15 with US Avastin and ABP15 with EU Avastin, as well as for US and EU Avastin. Infliximab SB2 US and EU Pharmacokinetic Healthy Infliximab [2] Remicade analysis to volunteers clearance was (Samsung 5mg/kg investigate the (n=30) increased in Bioepis) impact of subjects with infliximab drug antibodies vs drug antibodies in without healthy subjects (12.89 ± 2.69 vs. receiving a single 9.90 ± 1.74 ml/h; dose of p< 0.0005). intravenous Elimination infliximab was reduced in those with ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p< 0.01). Serum infliximab measured at 8 weeks correlated closely with infliximab clearance (R2 = 0.5494; p\ 0.0001)
met the pre-specified acceptance criteria for the relevant pharmacokinetic/pharmacodynamic parameter endpoints. A summary of the results of these studies are presented in the table below (Table 1). Table 1: Summary of phase I pharmacokinetic studies of potential biosimilar medicines Biosimilar Candidate Reference Product Study Design Population PK Outcomes (and PD where reported) Immunogenicity Outcomes Reference Bevacizumab (Amgen) US and EU Avastin 1mg/kg Randomized, single-blind, three-arm, parallel- group study (1:1:1) Healthy male volunteers (n= 202) 90% CI for the ratio of treatment means for from time zero extrapolated to infinite time (AUCinf) and maximal plasma concentration (Cmax) were within the prespecified limits of 80- 125% for the comparisons of ABP15 with US Avastin and ABP15 with EU Avastin, as well as for US and EU Avastin. No anti-drug antibodies detected at baseline or at end of study [1] Infliximab SB2 (Samsung Bioepis) US and EU Remicade 5mg/kg Pharmacokinetic analysis to investigate the impact of infliximab antibodies in healthy subjects receiving a single dose of intravenous infliximab Healthy volunteers (n=30) Infliximab clearance was increased in subjects with antibodies vs without (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p< 0.0005). Elimination was reduced in those with ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p< 0.01). Serum infliximab measured at 8 weeks correlated closely with infliximab clearance (R2 = 0.5494; p\ 0.0001) [2] drug drug