1451P - A pharmacokinetics and pharmacodynamics equivalence trial of proposed pegfilgrastim biosimilar, MYL-1401H vs EU neulasta® and US neulast...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Supportive Measures
Presenter Cornelius Waller
Citation Annals of Oncology (2016) 27 (6): 497-521. 10.1093/annonc/mdw390
Authors C.F. Waller1, R. Tiessen2, T. Lawrence3, A. Shaw3, M. Liu3, R. Sharma4, M. Baczkowski5, M. Kothekar6, R. Dias7, A. Barve8, E. Pennella8
  • 1Department Of Haematology, Oncology And Stem Cell Transplantation, University Medical Centre Freiburg And Faculty Of Medicine, University of Freiburg, D-79106 - Freiburg/DE
  • 2Early Development Services, PRA Health Sciences, Zuidlaren/NL
  • 3Pharmacokinetics/drug Metabolism Dept., Mylan Pharmaceutical Inc., 26505 - Morgantown/US
  • 4Global Product Safety & Risk Management, Mylan, Hatfield/GB
  • 5Product Safety And Risk Management, Mylan, 26505 - Morgantown/US
  • 6Research & Development, Biocon Research Ltd, Bangalore/IN
  • 7Clinical Operations, Mylan GmbH, 8050 - Zürich/CH
  • 8Global Clinical Research, Mylan, 15317 - Canonsburg/US



MYL-1401H is a proposed biosimilar to the reference product Neulasta® (pegfilgrastim).


This single-center, randomized, double-blind, 3-period, 3-treatment, 3-way crossover trial was conducted in healthy adult male and female volunteers. The primary objective was to compare the PK and PD of MYL-1401H (A) and EU-Neulasta® (B) and US-Neulasta® (C). The subjects were randomized to one of the six possible treatment sequences to receive a single subcutaneous injection (2 mg) of either A or B or C in a 3-period, 3-way crossover design. The 2 mg dose has been shown in the literature to lie on the steep part of the PD dose-response curve and therefore most sensitive to detect and evaluate differences in a (PK/PD) trial in healthy volunteers. To test the bioequivalence, general linear models (GLM) of analysis of variance were performed on the PK parameters of the natural log-transformed AUC0-∞ and Cmax of pegfilgrastim. The equivalence for PD parameters was tested using the GLM model on AUC0-t and Cmax of absolute neutrophil count (ANC).


216 subjects (170 male and 46 female) were enrolled and 208 subjects (163 male and 45 female) were included in PK and PD analysis:

AUC0-∞ Cmax ANC AUC0-t ANC Cmax
90% CIa 90% CIa 95% CIb 95% CIb
A/B 97.7%-111% 98.4%-116% 95.9%-104.5% 96%-102.8%
A/C 93.5%-107% 90.7%-107% 97.4%-106.1% 96.6%-103.5%
C/B 97.9%-112% 99.8%-118% 94.3%-102.7% 96%-102.8%

a PK Equivalence established if 90% CI is within 80%-125%;

b PD Equivalence established if 95% CI is within 85-117.65. 210 [86% (A), 88% (B), 87% (C)] subjects experienced 1733 treatment-emergent adverse events (TEAEs) that were mild to moderate in severity except for one subject with severe and serious adverse event (appendicitis; unrelated). The most common (i.e., reported by ≥20% of the subjects) study drug related TEAEs were back pain (81%), headache (57%) and pain in extremity (32%).


These results confirm the PK and PD equivalence of MYL–1401H with EU-Neulasta® and US-Neulasta®. There were no significant safety concerns and no relevant differences in safety and tolerability between the treatments.

Clinical trial identification

EudraCT Number: 2014-002229-37 Sponsor Protocol Number: MYL-1401H-1001

Legal entity responsible for the study

Mylan GmbH


Mylan GmbH


C.F. Waller: Member of an advisory board with Mylan. R. Tiessen: Employee of PRA Health Sciences, the CRO performing the study. T. Lawrence: Employee of Mylan Inc. and own company stock. A. Shaw: Mylan full-time employee and stock in Mylan. M. Liu: Employee of Mylan. Mylan's stock ownership and Mylan issued stock options. R. Sharma: Employed by Mylan on full term permanent basis and Mylan stock ownership. M. Baczkowski: Employee of Mylan. Financial relationship with employer in the form of stock options, restricted stock units, and shares of Mylan in retirement account. M. Kothekar: Employed by Biocon Research Limited. R. Dias: Employee of Mylan GmbH. A. Barve: Mylan full-time employee and stock in Mylan. E. Pennella: Mylan employee and stocks of Mylan.