Patent expirations for biological products have prompted the development of biosimilars, which have comparable quality, safety and efficacy to a licensed biological medicine (the ‘reference’ medicine). HX575 (Binocrit®, epoetin alfa biosimilar) was approved in Europe in 2007 for the treatment of chemotherapy-induced anaemia (CIA).
The development and approval of HX575 included extensive analytical characterisation and comparison with the reference epoetin alfa, followed by a clinical development programme; this included phase I pharmacokinetic/pharmacodynamic studies to show bioequivalence to the reference medicine, and a confirmatory phase III study to confirm therapeutic effectiveness in CIA. Since approval, HX575 has been extensively used in real-world clinical practice.
An array of analytical methods confirmed the similarity of HX575 and the reference epoetin alfa in terms of primary protein structure, higher-order protein structure, isoform pattern, post-translational modifications, receptor binding and biological activity. Phase I studies showed that HX575 and the reference medicine were bioequivalent following intravenous and subcutaneous administration. In a confirmatory phase III study (n = 114), HX575 was effective in treating CIA in cancer patients, and had a safety profile consistent with the therapeutic class and as expected for the therapeutic area. Post-approval data are also available for a range of cancer types; positive results have been reported from a multi-centre retrospective clinical study, single-centre experiences from several countries, and a large-scale prospective observational study. No additional/unexpected safety issues have emerged after 10 years of pharmacovigilance. A pilot study has suggested that HX575 may also be effective for the treatment of anaemia in low-/intermediate-1 risk myelodysplastic syndromes.
As of Feb 2017, HX575 has generated >252,000 patient years’ experience in CIA worldwide. Accumulated data and experience over a decade are reassuring that HX575 is effective and well tolerated for the treatment of CIA in patients with different cancer types.
Clinical trial identification
Legal entity responsible for the study
M.S. Aapro: Consulting or Advisory Role: Sandoz Speakers\' Bureau: Sandoz Research funding: Sandoz A. Krendyukov, N. Höbel, A. Seidl: Employee of Hexal AG P. Gascón: Lectureship in Sandoz International GmbH sponsored events