Abstract
A pharmacodynamics (PD) and immunogenicity study was conducted to investigate biosimilarity of Pelmeg(®), a pegfilgrastim biosimilar to EU-authorized Neulasta(®). The multiple-dose, randomized, double-blind, two-sequence, and three-period cross-over study comprised 96 healthy male subjects, receiving Pelmeg (Test [T]) and Neulasta (Reference [R]) in a sequential manner (T-T-R vs R-R-T). Subjects were dosed with 3 mg pegfilgrastim, as this dose was previously shown to be in the ascending part of the dose-response curve for PD. The primary PD endpoint was the area under the effect curve (AUEC(0-last)) for absolute neutrophil count (ANC). The primary immunogenicity endpoint was proportion of anti-drug antibody (ADA)-positive subjects at the end of Period 2 (ie, after administration of two doses of the same study drug). Comparability was demonstrated for the PD endpoint, with the geometric mean ratio (T/R) of AUEC(0-last) being 101.59%, with a corresponding 95% CI of [99.58; 103.63]. Of note, when using tighter acceptance limits (90.00%-111.00%), comparability between test and reference was shown as well. Only two confirmed ADA positive samples were detected, one after treatment with Pelmeg and one after Neulasta. These had a low ADA titer, no filgrastim reactivity, and no neutralizing capacity. No clinically meaningful differences in safety between Pelmeg and Neulasta were observed. Overall, the results from this study confirmed the biosimilarity of Pelmeg and Neulasta for PD and immunogenicity, as shown already at the bioanalytical level and in the pivotal PK/PD study with Pelmeg.