Published in:
Open Access 01-07-2020 | Pharmacodynamics | Original Research
PF-06881894, a Proposed Biosimilar to Pegfilgrastim, Versus US-Licensed and EU-Approved Pegfilgrastim Reference Products (Neulasta®): Pharmacodynamics, Pharmacokinetics, Immunogenicity, and Safety of Single or Multiple Subcutaneous Doses in Healthy Volunteers
Published in: Advances in Therapy | Issue 7/2020
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Introduction
PF-06881894 is a proposed biosimilar to pegfilgrastim
(Neulasta®). This study evaluated the
pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of
PF-06881894 vs pegfilgrastim reference products (US- and
EU-Neulasta®) in healthy volunteers.
Methods
A phase 1, open-label, randomized, crossover study was conducted to
assess the pharmacologic equivalence and safety of a single 6-mg dose of PF-06881894,
pegfilgrastim-US, and pegfilgrastim-EU. The primary PD endpoints were area under the
effect-versus-time curve for absolute neutrophil count (ANC) from dose administration
to 288 h postdose, and maximum observed ANC value among subjects confirmed negative
for anti-pegfilgrastim antibodies. Primary PK variables included area under the serum
pegfilgrastim-versus-time curve from the time of dose administration to time infinity
and maximum observed serum pegfilgrastim concentration. A second phase 1, open-label,
randomized (1:1), parallel-group, non-inferiority study was conducted to assess the
immunogenicity and safety of multiple 6-mg doses of PF-06881894 versus
pegfilgrastim-US. The primary endpoint for the immunogenicity study was the
proportion of subjects with both negative baseline and confirmed positive postdose
anti-pegfilgrastim antibodies at any time during the study.
Results
Across the single- and multiple-dose studies (N = 153 and N = 420 treated
subjects, respectively), demographics for age (18–65 years), male gender (n = 264/573), and white race (n = 423/573) were similar. Three-way PD/PK equivalence of PF-06881894,
pegfilgrastim-US, and pegfilgrastim-EU was demonstrated with the primary PD endpoints
and primary PK variables being completely contained within the predefined 90%
confidence interval acceptance limits (80–125%). The non-inferiority of PF-06881894
versus pegfilgrastim-US in terms of immunogenicity was established according to the
prespecified non-inferiority margin (≤10%). Overall, there were no clinically
meaningful differences in safety profiles among or between study groups.
Conclusions
Single-dose PF-06881894 demonstrated PD/PK equivalence and comparable
safety with US- and EU-pegfilgrastim reference products. Multiple-dose PF-06881894
demonstrated immunogenicity non-inferiority to pegfilgrastim-US with comparable
safety. Both studies contributed to the totality of evidence supporting
biosimilarity.
Trial Registration
ClinicalTrials.gov identifiers: NCT02629289 (C1221001); NCT03273842
(C1221005).