Comparative PK/PD study in healthy subjects demonstrates biosimilarity between pegfilgrastim biosimilar Pelmeg® and Neulasta®
Pegfilgrastim (EU-approved Neulasta®) is widely used for prevention of chemotherapy-induced neutropenia in patients with cancer. This study investigated PK/PD comparability of a new pegfilgrastim biosimilar (Pelmeg®) versus Neulasta® in healthy subjects.
Neutropenia, defined as an absolute neutrophil count (ANC) <0.5 x 109 cells/L, is an important limiting factor in the application of myelosuppressive chemotherapy in cancer patients. Duration of neutropenia and the ANC nadir are correlated with the development of infectious complications, which can necessitate chemotherapy dose reductions, compromise tumour control, and adversely affect patient survival.
Pegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) analogue indicated for the prevention of neutropenia in this setting. This first-in-human study looked at the pharmacokinetics (PK) and pharmacodynamics (PD) of Pelmeg® (development code B12019), a novel biosimilar version of pegfilgrastim, with the aim of confirming comparability to the reference product (EU-approved pegfilgrastim; Neulasta®). Safety and immunogenicity, as detected by anti-drug antibody (ADA) assay, were also analysed. The study featured a two-way cross-over design whereby patients were randomised to receive Pelmeg followed by Neulasta or vice versa.
Analysis of PK endpoints showed no relevant difference in exposure of pegfilgrastim after administration of Pelmeg® or Neulasta®. Hence, PK comparability between test and reference products was shown. ANC profiles were very similar after administration of Pelmeg® or Neulasta®. Following administration of either drug, mean ANC increased and reached a peak 3.5 days post-dose, decreasing thereafter and reaching pre-dose level at around day 18. No difference in ANC was seen between either drug. The percentage of subjects with adverse events was comparable for both Pelmeg® and Neulasta®, and no clinically relevant ADA signals were detected. Pelmeg® was found to be highly similar to the reference product.
Pelmeg®, a pelgrastim biosimilar, was found to have comparable absolute neutrophil PK and PD properties to its reference product.