Biosimilar Erythropoietin Research Articles

Multivariate statistics for the differentiation of erythropoietin preparations based on intact glycoforms determined by CE-MS

Owing to the increasing number of erythropoietin biosimilars being approved, the comparison of different erythropoietin preparations in the pharmaceutical area is gaining in importance. Erythropoietin has a distinct natural heterogeneity arising from its glycosylation, which shows strong composition variations. This heterogeneity increases the complexity of the analysis of erythropoietin considerably, but may also be used to distinguish different preparations. Here, a method is presented for the differentiation of various erythropoietin preparations by capillary electrophoresis-mass spectrometry and the subsequent application of multivariate statistics. Relative peak areas of selected intact erythropoietin isoforms were used as variables in principal component analysis and hierarchical agglomerative clustering. Both of these strategies were suited for the clear differentiation of all erythropoietin preparations, including marketed products and preproduction preparations, which differ in the manufacturer, the production cell line, and the batch number. By this means, even closely related preparations were distinguished on the basis of the combined information on the antennarity, the sialoform, and the acetylation of the observed isoforms.

Erythropoietin biosimilars currently available in hematology-oncology

The discovery of epoietin (EPO) and the cloning of its gene facilitated the understanding of the mechanism of control behind red blood cell formation. This cloning was followed by the commercial development of recombinant human EPO (rHuEPO). The use of erythropoiesis-stimulating agents (ESAs) (epoietin, ESA, EPO) is important for the treatment of anemia in patients with chronic renal failure and cancer patients with chemotherapy-induced anemia. After several years of discussions, debates and questions, ESA, intravenous iron and blood transfusions seem to have finally found their respective indications in the treatment of anemia in cancer patients receiving chemotherapy. Now, a new question arises: What is the role of ESA biosimilars?

Effective pharmaceutical regulation needs alignment with doctors

Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining approval criteria for biosimilar erythropoietins, which have been recently adopted. We observed an absence of the organised medical community in the public process of creating and updating the guidelines. In this article we argue that, to ensure that innovative medicines continue to find their way to the patients who might benefit from them, a closer collaboration between the organised medical community and regulators is needed.

Systematic review of toxicities of lineage-specific hematopoietic growth factors toxicities: Implications for biosimilar erythropoietins, thromopoietic receptor agonists, and continuous erythropoietin receptor agonists

e20733 Background: Erythropoiesis stimulating agents (ESAs) and the granulocyte and granulocyte macrophage colony stimulating factors (G-CSF/GM-CSF) have been widely used for the past two decades. Recently, thrombopoietin receptor agonists, romiplostim and eltrombopag, biosimilar erythropoietins, and a continuous erythropoietin receptor agonist were licensed. Although lineage specific hematopoietic growth factors play important roles in the treatment of cancer and chronic kidney disease, recent basic and clinical research studies have identified toxicities. Herein, we compared toxicities of ESAs, thrombopoietins and G-CSF/CSFs and the implications of these findings. Methods: Meta-analyses, reviews, clinical guidelines, and FDA transcripts for G-CSF, GM-CSF, and ESAs were reviewed. For MGDF, romiplostim, and eltrombopag, clinical trial reports, reviews, and FDA transcripts were reviewed. The study period was 2000 to 2008. Results: See Table . Conclusions: Commonalities in toxicities exist across lineage specific hematopoietic growth factors. Delayed recognition of adverse effects with ESAs and G-CSF highlights the importance of anticipating toxicities with biosimilars and thrombopoietin receptor agonists. [Table: see text] No significant financial relationships to disclose.

Règles d'utilisation des biosimilaires: Propositions consensuelles de la Société de néphrologie, de la Société francophone de dialyse et de la Société de néphrologie pédiatrique

Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining approval criteria for biosimilar erythropoietins, which have been recently adopted. We observed an absence of the organised medical community in the public process of creating and updating the guidelines. In this article we argue that, to ensure that innovative medicines continue to find their way to the patients who might benefit from them, a closer collaboration between the organised medical community and regulators is needed.