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

Background

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

Methods

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 AUC_0-∞ and C_max of pegfilgrastim. The equivalence for PD parameters was tested using the GLM model on AUC_0-t and C_max of absolute neutrophil count (ANC).

Results

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

^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%).

Conclusions

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

Funding

Mylan GmbH

Disclosure

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.