FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation.
OBJECTIVE
On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval.


METHODS
The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of > or = 5 x 10(6) CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or > or = 6 x 10(6) CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM.


RESULTS
The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of > or = 5 x 10(6) CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of > or = 6 x 10(6) CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia.


CONCLUSIONS
This report describes the Food and Drug Administration review supporting the approval of plerixafor.
Office of Oncology Drug Products, Office of New Drugs, Michael Brave U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA. michael.brave@fda.hhs.gov
Michael
M
Brave
Ann
A
Farrell
Sue
S
Ching Lin
Terrance
T
Ocheltree
Sarah
S
Pope Miksinski
Shwu-Luan
SL
Lee
Haleh
H
Saber
Jeanne
J
Fourie
Christoffer
C
Tornoe
Brian
B
Booth
Weishi
W
Yuan
Kun
K
He
Robert
R
Justice
Richard
R
Pazdur
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis; D001596:Benzylamines; D002986:Clinical Trials as Topic; D000080027:Cyclams; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D010919:Placebos; D011358:Product Surveillance, Postmarketing; D016032:Randomized Controlled Trials as Topic; D019718:Receptors, CXCR4 / Q000378:metabolism; D014481:United States; D014486:United States Food and Drug Administration
D018952:Antigens, CD34; D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D010919:Placebos; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor