B12019 is being developed as a biosimilar to Neulasta (INN pegfilgrastim), a pegylated, long-acting form of recombinant human granulocyte-colony stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia. A clinical development program, based on scientific advice from EMA, consisting of two clinical studies was conducted with B12019 to confirm the biosimilarity to EU-authorised Neulasta as established by analytical, functional and preclinical data. Pharmacokinetic (PK) and pharmacodynamic (PD) comparability between Neulasta and B12019 had been shown in a previous study (Blood 2016 128:5079). Here, the results of the second clinical study are presented.
Study B12019-102 investigated the immunogenicity and PD comparability of B12019 and Neulasta at a reduced dose (3 mg). This dose was selected because it is considered more sensitive to detect potential differences in PD between B12019 and Neulasta as compared to the clinical dose of 6 mg. The study was designed as a multiple-dose, randomized, double-blind, three-period, two-sequence cross-over study in 96 healthy volunteers. A hierarchical ADA test strategy with a highly sensitive screening assay followed by four parallel epitope-specific, confirmatory assays was established. Primary study endpoints were AUEC0-last of the absolute neutrophil count (ANC) for PD after cross-over and anti-drug antibody rate (ADA) for immunogenicity after repeat dosing.
The number of ADA-positive subjects was very low for both, B12019 and Neulasta. No imbalance was observed between the study drugs after repeated dosing.
Neither anti-filgrastim nor neutralising antibodies were detected for B12019 or Neulasta.
82 subjects were included in the model-based PD comparison. PD comparability was demonstrated, with the AUEC0-last geometric mean ratio with a 95% CI of 99.58; 103.63 being within the pre-specified acceptance range.
No clinically meaningful differences in the safety profile for B12019 and Neulasta were observed.
Study B12019-102 confirmed the PD comparability of B12019 with Neulasta at a sensitive dose of 3 mg.
The immunogenicity profile of B12019 did not show differences to Neulasta.
The study confirmed the biosimilarity of B12019 and Neulasta in a sensitive study design for immunogenicity and PD.
Roth, Né Meyer: Cinfa Biotech: Employment. Wessels: Cinfa Biotech: Employment. Hoefler: Staburo GmbH: Employment. Jankowsky: Cinfa Biotech: Employment.
Asterisk with author names denotes non-ASH members.