Clinical safety of biosimilar recombinant human erythropoietins

Abstract

Introduction: A “biosimilar” or “similar biological medicinal product” is a biological agent that is similar in terms of quality, safety, and efficacy to an authorized reference biological medicine. Since the expiration of the epoetin alfa patent in Europe, three agents have received marketing authorization from the European Medicines Agency: Binocrit (epoetin alfa; aka Abseamed and Epoetin Alfa Hexal), Retacrit (epoetin zeta; aka Silapo), and Eporatio (epoetin theta; aka Biopoin and Ratioepo).

Areas covered: Using the EMA dossiers and journal publications, this article reviews clinical safety data for these products, with emphasis on serious/severe adverse events and a special consideration of immunogenicity, venous thromboembolism, and mortality.

Expert opinion: A review of the available safety evidence shows that all three agents discussed have similar safety profiles. None were statistically higher on safety parameters to what is known about ESA as a class, when stratified by population. As with ESAs in general, immunogenicity, venous thromboembolism, and mortality are all concerns. What is known about ESAs regarding safety can be extended to biosimilar erythropoietins. Since biosimilars are unique, complex biological molecules, safety profiles may evolve from common to 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 effectiveness and safety profiles. Statistically, out of the commercially available formulations of the three products reviewed, no single product is less or more safe.

Keywords::

• biosimilars
• biosimilar pharmaceuticals
• drug safety
• erythropoietin
• recombinant proteins
• safety

Acknowledgements

Ivo Abraham was supported as Program Director of the AzAHEC Interprofessional Fellowship Program in Clinical Outcomes and Comparative Effectiveness Research, funded by the Bureau of Health professions, US Department of Health and Human Services. The authors thank two anonymous referees for their helpful comments and suggestions.

Declaration of interest

Both authors are employees of Matrix45, which has received research grants and contracts related to erythropoetic proteins from: Johnson & Johnson (Eprex®), Roche (NeoRecormon® and Mircera®), Amgen (Epogen®, Aranesp®) and Sandoz/Novartis (Binocrit®). By company policy, employees cannot hold equity in sponsor organizations except through mutual funds, and cannot receive direct personal benefits, financial or other, from sponsor organizations. Matrix45 is currently contracted for scientific consulting services with Sandoz/Novartis on an observational study on Binocrit® in the hemodialysis setting and both authors are involved in this work. Matrix45 provides similar services to other biopharmaceutical companies without exclusivity constraints. Manufacturers of the products reviewed here were not contacted for data, publications, or other sources of information, nor did they have any input on the review activities or in the preparation of the manuscript.

Notes

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