Neulasta Randomized, Healthy PK: After the first [3] (EU and US) volunteers 90%CI for the ratio treatment period three-way between the the proportion of 216 subjects crossover geometric means subjects with received at of the least one dose from anti-drug time zero antibodies 208 subjects extrapolated to (excluding ADA received at infinite time positive at baseline) least two of (AUCinf), and was: the three maximal plasma doses MYL-1401H: concentration 14 of 63 (22%) (Cmax) were within the predefined Neulasta (EU): bioequivalence 16 of 68 (24%) interval of Neulasta (US): 21 of 69 (30%) PD: 95% CI for the ratios of geometric means for the area under the curve above baseline for absolute neutrophil counts (ANC AUC0−t) and maximum change from baseline for ANC (ANC Cmax) were within the predefined PD equivalence interval of 0.8500 to 1.1765 Trastuzumab HD201 Herceptin Randomized, Healthy male 90%CI for the ratio No subjects were [4] (EU) blinded, subjects (n=73, between the positive for randomised geometric means drug antibodies on comparative PK 1:1) of the day 22 or 85 study from time zero extrapolated to infinite time (AUCinf), was within the predefined bioequivalence interval of An additional extension study to a phase I trial of rituximab was also reported and is described below.
Neulasta (EU and US) Randomized, three-way crossover Healthy volunteers 216 subjects received at least one dose 208 subjects received at least two of the three doses PK: 90%CI for the ratio between the geometric means of the from time zero extrapolated to infinite time (AUCinf), and maximal plasma concentration (Cmax) were within the predefined bioequivalence interval of PD: 95% CI for the ratios of geometric means for the area under the curve above baseline for absolute neutrophil counts (ANC AUC0−t) and maximum change from baseline for ANC (ANC Cmax) were within the predefined PD equivalence interval of 0.8500 to 1.1765 After the first treatment period the proportion of subjects with anti-drug antibodies (excluding ADA positive at baseline) was: MYL-1401H: 14 of 63 (22%) Neulasta (EU): 16 of 68 (24%) Neulasta (US): 21 of 69 (30%) [3] Trastuzumab HD201 Herceptin (EU) Randomized, blinded, comparative PK study Healthy male subjects (n=73, randomised 1:1) 90%CI for the ratio between the geometric means of the from time zero extrapolated to infinite time (AUCinf), was within the predefined bioequivalence interval of No subjects were positive for antibodies on day 22 or 85 [4] An additional extension study to a phase I trial of rituximab was also reported and is described below. drug
biosimilars-literature-review-june-2018.docx