Pharmacokinetics and Pharmacodynamics of a Proposed Pegfilgrastim Biosimilar MSB11455 Versus the Reference Pegfilgrastim Neulasta in Healthy Subjects: A Randomized, Double-blind Trial

Jason Lickliter; Radmila Kanceva; Emmanuelle Vincent; Armin Schueler; Eleanor Harrison-Moench; Corinne Seng Yue; Michael Stahl; Martin Ullmann; Vishal Ghori; Paul Griffin

doi:10.1016/j.clinthera.2020.05.020

Pharmacokinetics and Pharmacodynamics of a Proposed Pegfilgrastim Biosimilar MSB11455 Versus the Reference Pegfilgrastim Neulasta in Healthy Subjects: A Randomized, Double-blind Trial

Clin Ther. 2020 Aug;42(8):1508-1518.e1. doi: 10.1016/j.clinthera.2020.05.020. Epub 2020 Jul 11.

Authors

Affiliations

¹ Nucleus Network, Melbourne, Australia.
² Biosimilars, Fresenius Kabi SwissBioSim, Eysins, Switzerland. Electronic address: Radmila.Kanceva@fresenius-kabi.com.
³ Biosimilars, Fresenius Kabi SwissBioSim, Eysins, Switzerland.
⁴ Biostatistics, Merck Healthcare, Darmstadt, Germany.
⁵ Quantitative Pharmacology, Merck Healthcare, Darmstadt, Germany.
⁶ Learn and Confirm, Inc., St-Laurent, Québec, Canada.
⁷ School of Medicine, University of Queensland, Brisbane, Australia; Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Queensland, Australia.

PMID: 32660769
DOI: 10.1016/j.clinthera.2020.05.020

Abstract

Purpose: MSB11455 is a proposed biosimilar to the reference pegfilgrastim (Neulasta®). This pivotal equivalence study (NCT03251248) assessed the pharmacokinetic and pharmacodynamic equivalence of MSB11455 to the reference product.

Methods: This 2-way, 2-sequence, group-sequential, crossover study was conducted in healthy subjects. Subjects received a single subcutaneous dose of MSB11455 or the reference product (both 6 mg/0.6 mL) on Day 1 of each study period. Pharmacokinetic and pharmacodynamic (absolute neutrophil count; ANC) samples were taken predose and up to day 16 post-dose. Non-compartmental parameters were calculated. Immunogenicity samples were taken pre-dose and up to day 84 after the first dose. Safety was assessed throughout the study.

Findings: A total of 292 subjects were randomized to therapy and treated; 244 received both treatments. For all primary pharmacokinetic and pharmacodynamic parameters, 90% repeated confidence intervals of geometric means ratio of MSB11455 to the reference product were within the pre-defined equivalence range (80.00%-125.00%) for AUC_0-∞ (96.59-112.82); AUC_0-last (97.29-113.96), C_max (97.13-114.99), maximum observed effect on ANC (98.74-102.39), and area under the effect-time curve from time zero to time to last quantifiable concentration (97.30-100.23). Safety, tolerability, and immunogenicity were comparable between treatments. No filgrastim-specific neutralizing antibodies were detected with either treatment sequence.

Implications: Pharmacokinetic and pharmacodynamic equivalence of MSB11455 and the reference product was shown, with comparable immunogenicity, safety, and tolerability between treatments. The study supports the biosimilarity of MSB11455 to the reference product. ClinicalTrials.gov identifier: NCT03251248.

Keywords: MSB11455; bioequivalence; biosimilarity; pegfilgrastim; pharmacodynamics; pharmacokinetics.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Area Under Curve
Biosimilar Pharmaceuticals / pharmacokinetics*
Biosimilar Pharmaceuticals / pharmacology*
Cross-Over Studies
Double-Blind Method
Female
Filgrastim / pharmacokinetics*
Filgrastim / pharmacology*
Healthy Volunteers
Humans
Leukocyte Count
Male
Middle Aged
Neutrophils / drug effects*
Polyethylene Glycols / pharmacokinetics*
Polyethylene Glycols / pharmacology*
Therapeutic Equivalency
Young Adult

Substances

Biosimilar Pharmaceuticals
pegfilgrastim
Polyethylene Glycols
Filgrastim

Associated data

ClinicalTrials.gov/NCT03251248