The World Marrow Donor Association (WMDA) has expressed its position on the use of granulocyte colony-stimulating factor (G-CSF) biosimilars in healthy donors in an article published in the journal Haematologica [1].
Human G-CSF is a single polypeptide chain protein of 174 amino acids with O-glycosylation at one threonine residue. G-CSF has the effect of increasing the production and function of neutrophils in the blood. It is a physiologically active protein that is used for the treatment of neutropenia–a low number of neutrophils–caused by cancer chemotherapy or bone marrow transplantation.
Two brand-name recombinant G-CSFs, Neupogen (filgrastim, produced in Escherichia coli) and Granocyte (lenograstim, produced in Chinese hamster ovary cells) are in clinical use. Both are licensed for mobilization of human stem cells in normal donors in the EU.
Prior to the availability of G-CSF, donors could only donate bone marrow. However, over the last 10 years there has been a marked shift from the donation of bone marrow to peripheral blood stem cells (PBSCs), due largely to donor preference. In fact in 2010, according to WMDA, 9,248 unrelated donors donated G-CSF mobilized PBSCs.
The first biosimilar G-CSF was licensed by EMA in 2008, and there are currently six biosimilar G-CSF products licensed for use in the EU [2]. All of these biosimilars are also approved for haematopoietic stem cell transplantation.
WMDA is concerned about the use of biosimilar G-CSF in healthy donors who donate PBSCs, given that this indication was obtained by extrapolation of clinical data rather than by a dedicated clinical study. WMDA believes that this ‘may raise concerns for the allogeneic transplant recipient, particularly if the mobilized product differs from that expected with the reference product’.
WMDA therefore recommends that since there has been ‘little safety analysis and no long-term follow up’ that these G-CSF biosimilars ‘not be used for mobilization in normal donors unless the donor is followed on a study looking at this question with both the recipient and the donor providing appropriate consent’.
This viewpoint has, however, been questioned by GaBI Journal author Christian Schneider [3], who reminds us that regulatory authorities approve biosimilars based on the fact that their efficacy and safety are comparable to those of the reference product. Biosimilars are also subjected to the same stringent regulations post-approval as brand-name biologicals when it comes to quality.
A recent study by German researchers has also demonstrated the ‘similarity’ of biosimilar G-CSF (Biograstim, Ratiograstim or Tevagrastim) in terms of efficacy and safety compared to reference G-CSF (Neupogen) for mobilization of stem cells in healthy donors [4].
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References
1. Shaw BE, Confer DL, Hwang WY, Pamphilon DH, Pulsipher MA. Concerns about the use of biosimilar granulocyte colony-stimulating factors for the mobilization of stem cells in normal donors: position of the World Marrow Donor Association. Haematologica. 2011 Jul;96(7):942-7.
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2013 Feb 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe
3. Schneider CK. The ethics of biosimilars. Generics and Biosimilars Initiative Journal (GaBI Journal). 2013;2(1).6-7. doi:10.5639/gabij.2013.0201.001
4. GaBI Online - Generics and Biosimilars Initiative. Mobilization of stem cells in healthy donors by G-CSF biosimilars shows comparable efficacy and safety to Neupogen [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2013 Feb 8]. Available from: www.gabionline.net/Biosimilars/Research/Mobilization-of-stem-cells-in-healthy-donors-by-G-CSF-biosimilars-shows-comparable-efficacy-and-safety-to-Neupogen
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