Abstract P3-14-10: Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects
Authors: Nakov R , Gattu S , Wang J , Velinova M , Skerjanec A 
Published: February 2018

Background: Granulocyte colony-stimulating factors such as filgrastim and its long-acting version pegfilgrastim are widely used to prevent neutropenia in patients receiving chemotherapy. LA-EP2006 is a proposed biosimilar pegfilgrastim that has been compared with reference pegfilgrastim and shown to have no clinically meaningful differences regarding efficacy and safety in breast cancer patients receiving myelosuppressive chemotherapy.1,2

Methods: This single-dose, randomized, double-blind, two-way crossover study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and safety of LA-EP2006 and reference pegfilgrastim (Neulasta®, Amgen)in healthy male and female subjects. Subjects were randomized to receive a single 6 mg subcutaneous (sc) injection of LA-EP2006 or reference on Day 1. After dosing, subjects underwent a 4-week assessment period followed by a 4-week washout period before crossing over to receive the other pegfilgrastim and were assessed for a further 4 weeks. The primary objective was to determine PK similarity of LA-EP2006 and reference pegfilgrastim (AUC0→∞, AUC0→last and Cmax),and then PD similarity (absolute neutrophil count [ANC] response in terms of AUEC(0-last) and Emax). Secondary objectives included safety and immunogenicity.

Results: A total of 92 subjects were randomized to receive LA-EP2006 then reference (LA-EP2006/reference), and 93 subjects were randomized to receive reference then LA-EP2006 (reference/LA-EP2006) with one subject enrolled but not receiving study medication. A total of 169 subjects were included in the PK and PD analyses. Demographics and baseline characteristics were similar between groups in both treatment periods. PK similarity was shown since the 90% confidence interval (CI) for the geometric mean ratio of LA-EP2006 vs. reference was within the predefined similarity range 0.8-1.25. PD similarity was shown since the 95% CI for the ratio of LA-EP2006 vs. reference was within the predefined similarity range 0.8-1.25 (Table). Secondary endpoints and safety were similar between groups. No neutralising antibodies were detected.

PK and PD parameters for the comparison between LA-EP2006 and reference pegfilgrastim (N=169)*.ParameterGeometric LS meansPoint EstimateCI LA-EP2006Reference LowerUpperPK (serum concentration)   90% CIAUC0→–(ng*h/mL)765267301.13701.05591.2244AUC0→last (ng*h/mL)748765741.14351.06071.2328Cmax (ng/mL)2091891.10821.03121.1909PD (ANC)95%CIAUEC0→last398739271.01550.99481.0366Emax32.632.70.99510.97371.0169*N=168 for AUC0→–; ANC, absolute neutrophil count; AUC0→–, area under curve measured from the time of dosing and extrapolated to infinity; AUC0→last, area under curve measured from time of dosing to last measurable concentration; AUEC0→last, area under effect curve measured from time of dosing to last measureable concentration; Cmax, measured maximum serum concentration after administration; Emax, maximum effect attributable to study drug; PD, pharmacodynamics; PK, pharmacokinetics.

Conclusions: This study shows similar PK, PD and safety of LA-EP2006 to the reference pegfilgrastim.

References:

1. Harbeck et al. 2016;12:1359-67.

2. Blackwell et al. 2016;21:789-94.

Citation Format: Nakov R, Gattu S, Wang J, Velinova M, Skerjanec A. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-10.