GP2015 EU Enbrel Randomised, Healthy adult 90% CIs of the All samples from the [10] Etanercept 50mg double-blind, male geometric mean ratios pre-dose (Day 1) (Hexal) single-dose, volunteers of AUClast, AUCinf and point in each study Pre-Filled crossover (n=54; Cmax were within the period were ADA Syringe study 54PPP) prespecified negative. acceptance criteria of Three subjects had a 80-125%. confirmed neutralising ADA response at the follow up visit (Day 29, Period 2) with a low titre close to the detection limit (treatment sequence GP2015/Enbrel). GP2015 GP2015 Randomised, Healthy 90% CIs of the No ADAs were detected Etanercept Etanercept open-label, male geometric mean ratios during the treatment single-dose, volunteers of AUClast, AUCinf and periods nor at the Autoinjector Pre-Filled crossover (n=51; Cmax were within the follow-up visit. Syringe study 48PPP) prespecified acceptance criteria of 80-125%. Filgrastim Pegfilgrastim Neulasta Randomised, Healthy adult 90% CIs of the No samples at the 0 [11] (Apotex) 6mg volunteers geometric mean ratios and 672 hr timepoints (n=66; of AUClast, AUCinf and (n=190) were identified single-dose, 49M/17F; Cmax were within the as ADA positive. crossover 56PPP) prespecified study acceptance criteria of 80-125%. 95% CIs of the geometric mean ratios of each of the PD parameters (ANC, AUECt, and Emax) were fully contained within the prespecified acceptance criteria of 80-125%. Biosimilar Reference Study PK Outcomes (and PD Immunogenicity Study Design Reference Candidate Product Population reported) Outcomes Human Growth Hormone
GP2015 Etanercept (Hexal) Pre-Filled Syringe EU Enbrel 50mg Randomised, double-blind, single-dose, crossover study Healthy adult male volunteers (n=54; 54PPP) 90% CIs of the geometric mean ratios of AUClast, AUCinf and Cmax were within the prespecified acceptance criteria of 80-125%. All samples from the pre-dose (Day 1) in each study period were ADA negative. Three subjects had a confirmed ADA response at the follow up visit (Day 29, Period 2) with a low titre close to the detection limit (treatment sequence GP2015/Enbrel). [10] GP2015 Etanercept Autoinjector GP2015 Etanercept Pre-Filled Syringe Randomised, open-label, single-dose, crossover study Healthy male volunteers (n=51; 48PPP) 90% CIs of the geometric mean ratios of AUClast, AUCinf and Cmax were within the prespecified acceptance criteria of 80-125%. No ADAs were detected during the treatment periods nor at the follow-up visit. Filgrastim Pegfilgrastim (Apotex) Neulasta 6mg Randomised, single-dose, crossover study Healthy adult volunteers (n=66; 49M/17F; 56PPP) 90% CIs of the geometric mean ratios of AUClast, AUCinf and Cmax were within the prespecified acceptance criteria of 80-125%. 95% CIs of the geometric mean ratios of each of the PD parameters (ANC, AUECt, and Emax) were fully contained within the prespecified acceptance criteria of 80-125%. No samples at the 0 and 672 hr timepoints (n=190) were identified as ADA positive. [11] Biosimilar Candidate Reference Product Study Design Study Population PK Outcomes (and PD reported) Immunogenicity Outcomes Reference Human Growth Hormone neutralising point
biosimilars-literature-review-december-2016-update.docx