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

Abstract

Introduction: PF-06881894 is a proposed biosimilar to pegfilgrastim (Neulasta Ò). This study evaluated the pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of PF-06881894 vs pegfilgrastim reference products (US-and EU-Neulasta Ò) 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 Digital Features To view digital features for this article go to

Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer

“…The results for platelet counts were consistent with those for US-and EU-pegfilgrastim reference products. Results for PF-06881894 in healthy volunteers demonstrated return of counts to baseline levels by follow-up visit [25], and was also demonstrated in Phase II of this study. In addition, the observed clinical laboratory findings and safety profile were consistent with the known therapeutic response for the USand EU-approved pegfilgrastim reference product (Neulasta) [25,37].…”

“…The methodology for antibody detection (Online Resource Methods S1) has been described previously by Moosavi et al . [ 25 ].…”

Analysis of the Regulatory Science Applied to a Single Portfolio of Eight Biosimilar Product Approvals by Four Key Regulatory Authorities

“…They are also key to guiding the requirement for, and nature of, subsequent comparative clinical studies [ 31 ]. The proportion of PK/PD queries was unaffected whether the study was conducted in patients (such as for PF-rituximab [ 32 ]) or in healthy subjects (PF-infliximab [Ixifi ™ ] [ 33 ], PF-epoetin [ 34 , 35 ], PF-filgrastim [ 36 ], PF-trastuzumab [ 37 ], PF-bevacizumab [ 38 ], PF-adalimumab [Abrilada ™ /Amsparity] [ 39 ], PF-pegfilgrastim [Nyvepria ™ ] [ 40 ]). The generally low focus on PK information across RAs may reflect the proactive engagement of the applicant with the relevant RA during the study design process, the transparency of the data disclosure and interpretation.…”

Pegfilgrastim Biosimilars: Where Are We Now?

“…US pegfilgrastim. Pegfilgrastim-apgf was shown to be noninferior to US pegfilgrastim, and there was no clinically meaningful difference in safety between the two study groups ( Moosavi et al, 2020 ).…”