New G-CSF agonists for neutropenia therapy.
BACKGROUND
Granulocyte colony-stimulating factor (G-CSF; filgrastim) and its pegylated form (pegfilgrastim) are widely used to treat neutropenia associated with myelosuppressive chemotherapy and bone marrow transplantation, AIDS-associated or drug-induced neutropenia, and neutropenic diseases. G-CSF facilitates restoration of neutrophil counts, decreases incidence of infection/febrile neutropenia and reduces resource utilization. G-CSF is also widely used to mobilize peripheral blood stem cells for hematopoietic transplant.


METHODS
We review the therapeutic use, cost effectiveness and disease impact of G-CSF for neutropenia, development of G-CSF biosimilars and current next-generation discovery efforts.


CONCLUSIONS
G-CSF has impacted the treatment and survival of patients with congenital neutropenias. For chemotherapy-associated neutropenia, cost effectiveness and impact on survival are still unclear. G-CSFs are expensive and require systemic administration. Market entry of new biosimilars, some with enhanced half-life profiles, will probably reduce cost and increase cost effectiveness. There is no evidence that marketed or late development biosimilars display effectiveness superior to current G-CSFs. Second-generation compounds that mimic the activity of G-CSF at its receptor, induce endogenous ligand(s) or offer adjunct activity have been reported and represent attractive G-CSF alternatives, but are in preclinical stages. A significant therapeutic advance will require reduced depth and duration of neutropenia compared to current G-CSFs.
Harvard University, Massachusetts General Hospital, Department of Stem Cell and Regenerative Medicine/Center for Regenerative Medicine , 185 Cambridge Street, CPZN 4400, Boston, MA 02114 , USA.
Jonathan
J
Hoggatt
Louis M
LM
Pelus
D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000819:agonists*; D006801:Humans; D009503:Neutropenia / Q000188:drug therapy*
D059451:Biosimilar Pharmaceuticals; D016179:Granulocyte Colony-Stimulating Factor