Clinical safety of biosimilar recombinant human granulocyte colony-stimulating factors

Abstract

All three agents have similar safety profiles. None were statistically higher on safety parameters to what is known about originator filgrastim (Neupogen). What is known about filgrastim in general regarding safety can be extended to biosimilar filgrastim. Safety profiles may become more differentiated once long-term product-specific safety data are available. Large-sample, long-term, observational studies of real-world practice will provide the heterogeneity and statistical power to demonstrate product-specific safety profiles. Current evidence indicates that statistically no one product is less and no one product is more safe.

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

“…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]. As reference filgrastim and pegfilgrastim are similar in safety [9,10], we assumed filgrastim-sndz and pegfilgrastim to be similar in safety as well.…”

Biosimilars in 3D

“…The manufacturing process is complex, consisting of choice of cell type, production, purification and formulation. 4,9 Hence, a biosimilar will never be the same as the reference product, only similar-and, preferably, as similar as possible.…”

“…This, in turn, has created significant clinical and economic opportunities for pharmaceutical companies to develop and seek marketing authorization for a number of biopharmaceuticals (e.g., human growth hormone, erythropoiesisstimulating agents [ESAs], granulocyte colony-stimulating factors [GCSFs])-and in the not-so-distant future, insulin, interferon β, recombinant follicle stimulating hormone and various monoclonal antibodies. [1][2][3] Drawing upon our work on the clinical efficacy and safety of biosimilar recombinant human erythropoietin [4][5][6][7][8] and filgrastim, [9][10][11] as evidenced in registration trials and post-approval studies, we review here three issues of relevance to the bioengineering field: (1) definition, (2) 4,13 There are biosimilars produced in less regulated markets; however, they are not considered in this article.…”

“…As we cautioned in our reviews 4,9 of biosimilar growth factors, to enable broader safety signal detection of adverse events with a lower incidence rate than what could be detected in Phase III trials, follow-on observational studies and registries with larger samples and greater heterogeneity of patients, clinicians and centers are warranted. Also helpful may be safety analyses from drug safety databases, claims databases and electronic health records.…”

“…In the worst case, the antibodies may neutralize the endogenous protein. More importantly, recent reviews 4 of the clinical safety of the three biosimilar recombinant human erythropoietins and the three biosimilar recombinant GCSFs approved by the EMA (and one biosimilar G-CSF approved by the FDA though the conventional BLA pathway) 9 found no differences in clinical safety profiles of these biosimilar agents relative to their originators in the respective classes.…”