Pharmacokinetic and pharmacodynamic bioequivalence study of a pegfilgrastim biosimilar INTP5 in healthy subjects

Abstract

Purpose

This study compared pharmacokinetics, pharmacodynamics, safety and immunogenicity profiles of INTP5 (a potential pegfilgrastim biosimilar) with that of Neulasta^®.

Methods

In this randomised, assessor-blind, crossover study, 344 healthy subjects received single subcutaneous dose of both INTP5 and Neulasta at 3 mg/0.3 ml (n = 172) or 6 mg/0.6 ml (n = 172) dose. The primary endpoints were AUC_0–t, AUC_0–∞ and C_max of pegfilgrastim; and AUEC_0–t and E_max of absolute neutrophil count (ANC).

Results

All 344 subjects dosed were included in the safety and immunogenicity analyses, and 292 subjects in the pharmacokinetic and pharmacodynamic analyses. At 6 mg dose, test to reference ratio (90% CI) of AUC_0–t was 105.65% (99.60–112.06%), AUC_0–∞ was 105.72% (99.55–112.28%) and C_max was 103.62% (98.19–109.35%); while test to reference ratio (95% CIs) of ANC AUEC_0–t was 100.79% (97.75–103.92%) and E_max was 98.70% (95.52–101.98%). Both the primary endpoints met the bioequivalence criteria (CIs within 80–125%). Similarly, at 3 mg dose, these endpoints were within the acceptance range of 80–125%. CD34+ profiles were similar and 95% CIs were within acceptance range at both doses. Adverse events were reported in 54 (15.7%; 8.72% in INTP5 vs. 8.39% in Neulasta) subjects; most events were mild. The incidences of anti-drug antibodies were low and similar between INTP5 and Neulasta and no neutralising antibodies were detected.

Conclusions

Pharmacokinetic and pharmacodynamic bioequivalence was established between INTP5 and Neulasta following 3 and 6 mg doses. Safety and immunogenicity profiles were similar between INTP5 and Neulasta.

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