3. A pharmacokinetics and pharmacodynamics equivalence trial of the proposed pegfilgrastim biosimilar, MYL-1401H, versus reference pegfilgrastim

Abstract –

Purpose: Pegfilgrastim is a long-acting granulocyte colony-stimulating factor indicated for prevention of febrile neutropenia in patients receiving myelosuppressive chemotherapy by promoting neutrophil recovery.

Methods: This phase 1, randomized, double-blind, three-way crossover trial in healthy volunteers evaluated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of the proposed biosimilar, comparing MYL-1401H, reference pegfilgrastim (Neulasta®, Amgen Inc, Thousand Oaks, CA, USA) sourced from the European Union, and reference pegfilgrastim sourced from the USA. Primary PK end points were peak plasma concentration of pegfilgrastim (Cmax) and area under the plasma concentration–time curve from the time of dosing to infinity (AUC0−inf). Primary PD end points were area under the curve above baseline for absolute neutrophil counts (ANC AUC0−t) and maximum change from baseline for ANC (ANC Cmax). Adverse events were also recorded.

Results: The primary PK and PD end points were similar across all groups. For the PK parameters, the 90% confidence intervals (CIs) of the ratios of geometric means ranged between 0.91 and 1.18, which were within the predefined bioequivalence interval of 0.8000 to 1.2500 for all comparisons. For the PD parameters, the 95% CIs of the ratios of geometric means ranged between 0.94 and 1.06 for all comparisons, which were within the predefined PD equivalence interval of 0.8500 to 1.1765. The safety profiles were similar, with the most common adverse events being back pain and headache.

Conclusions: MYL-1401H demonstrated similar PK, PD, and safety to reference pegfilgrastim in healthy volunteers and may be an equivalent option for the prevention of febrile neutropenia.

Funding: This study was funded by Mylan Inc, Canonsburg, PA, and Biocon Ltd, Bangalore, India.