1573P - Pharmacokinetic and pharmacodynamic comparability of B12019, a proposed pegfilgrastim biosimilar

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Pharmacology
Supportive Care
Palliative and Supportive Care
Presenter Karsten Roth
Citation Annals of Oncology (2017) 28 (suppl_5): v543-v567. 10.1093/annonc/mdx388
Authors K. Roth1, H. Wessels1, J. Hoefler2, R. Jankowsky3
  • 1Clinical Development, Cinfa Biotech, 80335 - Munich/DE
  • 2Biostatistics, Staburo, 81549 - Munich/DE
  • 3Management, Cinfa Biotech, 80335 - Munich/DE

Abstract

Background

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 was conducted with B12019 in comparison to EU-authorised Neulasta to confirm the biosimilarity as established by analytical, functional and preclinical data.

Methods

The clinical development program for B12019 consisted of two clinical studies. Study B12019-101 investigated pharmacokinetics (PK) and pharmacodynamics (PD) comparability of B12019 to Neulasta. The 6mg single-dose, randomised, double-blind, two-way crossover study enrolled 172 healthy volunteers. The primary PK endpoints were the area under the plasma concentration-time curve (AUC0-last) and the maximum concentration (Cmax) as well as the area under the effect curve (AUEC0-last) for absolute neutrophil count (ANC) for PD. In study B12019-102 immunogenicity and PD comparability of B12019 and Neulasta were investigated in a 3mg multiple-dose, randomised, double-blind, three-period, two-sequences crossover study in 96 healthy volunteers. Primary endpoints were AUEC0-last for PD and anti-drug antibody rate (ADA) for immunogenicity.

Results

Study B12019-101, using 6 mg, confirmed PK and PD comparability (compare also Roth et al, Blood, Dec 2016). In study B12019-102, 82 subjects were included in the model-based PD comparison. PD comparability was demonstrated, with the AUEC0-last geometric mean ratio with a CI of 99.6; 103.6 being within the pre-specified acceptance range. In both studies, no imbalance of ADA-positive samples after single or repeated dosing were observed. Neither anti-G-CSF nor neutralising antibodies were detected for B12019 or Neulasta.

Conclusions

· The clinical program confirmed the biosimilarity of B12019 and Neulasta in highly sensitive clinical study settings. · PK comparability of B12019 and Neulasta was demonstrated at the clinical dose of 6 mg. · PD comparability of B12019 and Neulasta was shown at the clinical dose of 6 mg and the reduced dose of 3 mg. · The safety and immunogenicity profile of B12019 did not show any clinically meaningful differences to Neulasta.

Clinical trial identification

NCT02912377 NCT02629562

Legal entity responsible for the study

Cinfa Biotech S.L., Olloki, Spain

Funding

Cinfa Biotech S.L., Olloki, Spain

Disclosure

K. Roth, H. Wessels, R. Jankowsky: Employee of Cinfa Biotech J. Hoefler: Employee of Staburo GmbH, statistical consultancy