Clinical experience with Zarzio® in Europe: what have we learned?

Abstract

Biosimilars are similar, but non-identical, versions of existing biological drugs for which patents have expired. Despite the rigorous approval process for biosimilars, concerns have been expressed about the efficacy and safety of these products in clinical practice. Biosimilars of filgrastim, based on the originator product Neupogen®, have been available since 2008 and are now in widespread clinical use in Europe and elsewhere. Three biosimilar G-CSFs have been approved based on a combination of physicochemical and biological protein characterisation, pharmacokinetic and pharmacodynamic assessment in healthy volunteers and efficacy and safety data in patients with cancer. To assess whether biosimilars are effective in the real-world clinical practice setting, a pooled analysis of five post-approval studies of biosimilar G-CSF (Zarzio®) that included 1,302 adult patients who received at least one cycle of chemotherapy with G-CSF support for the prevention of neutropenia was conducted. A total of 36 % of patients had a febrile neutropenia risk of >20 %, while 39.6 % had a risk of 10–20 % based on chemotherapy regimen. The occurrence of severe or febrile neutropenia was within the range of that observed in previous studies of originator G-CSF. In addition, the safety profile of Zarzio® was consistent with that reported for originator G-CSF and the known safety profile of G-CSF. Initial concerns about the use of biosimilars, at least with regard to biosimilar G-CSFs, appear to be unfounded. Adoption of cost-effective biosimilars should help reduce healthcare costs and improve patient access to biological treatments.

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz

“…Considering the evidence from the pivotal pegfilgrastim versus (reference) standard filgrastim noninferiority trials [9,10], prophylaxis with standard and pegylated filgrastim were considered to be similar to each other in efficacy. By triangulation, as filgrastim-sndz and reference filgrastim have been shown to be similar in efficacy, we assumed pegfilgrastim and filgrastim-sndz to be noninferior to each other as well [11][12][13]. Analogously, the safety profile of filgrastim-sndz was assumed to be the same as that of reference filgrastim [14].…”

Clinical considerations for the development of biosimilars in oncology

“…4,35,36 This is due, in part, to the projected savings in commercial development associated with the abbreviated approval process for biosimilars compared with novel biologic therapies. 37 Biosimilars have already improved access to wellestablished therapeutic interventions in Europe and other locations where approvals have occurred.…”

“…37 Biosimilars have already improved access to wellestablished therapeutic interventions in Europe and other locations where approvals have occurred. 4,35 Although there are some limitations to the use of biosimilars due to issues with interchangeability and extrapolation of data, in the long-term, biosimilars should offer a wider array of Non-clinical: similar structure, function, chromatographic profile, PK, and immunogenicity to trastuzumab sourced from US and EU 54 Phase 1: comparative PK, PD, safety, tolerability, and immunogenicity to trastuzumab sourced from US and EU, in healthy subjects 14 Mfg, manufacturer; PK, pharmacokinetics; PD, pharmacodynamics; HER2, human epidermal growth factor receptor 2; ORR, overall response rate; MBC, metastatic breast cancer www.tandfonline.com 291 mAbs therapeutic solutions and increase accessibility to effective cancer treatments. Clinicians should understand the importance of biosimilars in clinical practice and how to make informed decisions about their appropriate use.…”

Pharmacokinetic and pharmacodynamic properties of a new biosimilar filgrastim TPI G-CSF in comparison to the marketed reference filgrastim Neupogen®: a double-blind, single-dose, two-period crossover trial

“…22 Biosimilar agents, in general, have comparable safety and efficacy to approved reference products and may provide more affordable treatment options that offer increased access for the population at large. 6,23 The development and approval process for biosimilars is a highly structured, tier-based system wherein the developer is required to demonstrate a high level of analytical and functional similarity, non-clinical safety, formulation stability, dosage form safety, and other patient safety elements prior to conducting studies in human subjects to compare pharmacokinetics, pharmacodynamics, and immunogenicity.…”

“…4 The pharmacokinetic characteristics of filgrastim are widely reported. [5][6][7] The absorption is bi-segmental, and total body clearance of filgrastim follows a first-order pharmacokinetic model. 7 A positive linear correlation is demonstrated between the parenteral dose administered and the serum concentration, as well as the areas under the concentrationtime curves (AUCs).…”