FDA Approves Plerixafor to Improve Stem Cell Mobilization for Autologous Transplantation

Laurie Barclay, MD

December 17, 2008

December 17, 2008 — The US Food and Drug Administration has approved plerixafor (Mozobil, Genzyme), a novel small-molecule CXCR4 chemokine antagonist that enhances mobilization of stem cells for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Genzyme, the manufacturer, anticipates that the drug will be available in the United States in 2009.

"Mozobil is an important advancement in the treatment of patients with certain types of cancer who require a stem cell transplant," John F. DiPersio, MD, PhD, a professor at Washington University in St. Louis, Missouri, said in a news release. "This product should become an integral part of the treatment regimen for transplantation because of the benefits it offers to patients, physicians and transplant centers."

Plerixafor injection, which has also been granted orphan drug designation, is intended for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the bloodstream, where they can be collected.

Autologous transplantation requires at least 2 million stem cells per kilogram of body weight, which may take 3 or 4 hours during multiple days in some patients, and other patients are not able to reach this goal.

"For many cancer patients, moving on to a transplant is their only hope for remission or a cure," Dr. DiPersio said.

Pivotal phase 3 trials showed that the number of stem cells mobilized for collection was significantly increased in patients receiving plerixafor vs current standard of care, and that the time needed for patients to mobilize sufficient numbers of stem cells for autologous transplantation was decreased.

The target number of at least 5 million stem cells/kg body weight in 4 or fewer apheresis sessions was achieved in 59% percent of patients with NHL who received plerixafor and G-CSF vs 20% of patients who received placebo. The median number of days to reach this target stem cell count was 3 days for patients receiving plerixafor and was not evaluable in the placebo group.

The target number of at least 6 million stem cells/kg of body weight collected in 2 or fewer apheresis sessions was achieved in 72% of patients with MM who received plerixafor and G-CSF compared with 34% of those who received placebo. The median number of days to reach this target cell count was 1 vs 4 days, respectively. At 12-month follow-up, the plerixafor plus G-CSF and placebo plus G-CSF groups had comparable graft durability rates.

By decreasing the number of apheresis days, plerixafor may also provide economic benefits for transplant centers. Plerixafor may also decrease the number of patients needing a second mobilization procedure because of failure to mobilize sufficient numbers of stem cells with G-CSF alone.

Additional therapeutic indications for plerixafor under development may include mobilization of hematopoietic stem cells in allogeneic stem cell transplants and tumor sensitization in adult myeloid leukemia and other hematological cancer.

Treatment with plerixafor should begin after the patient has received G-CSF once daily for 4 days, approximately 11 hours before starting apheresis, for up to 4 consecutive days. The recommended dose is 0.24 mg/kg body weight by subcutaneous injection. The dose should not exceed 40 mg/day, based on increasing exposure with increasing body weight. If creatinine clearance is 50 mL/min or less, the plerixafor dose should be decreased by one third to 0.16 mg/kg.

Potential adverse effects of plerixafor may include tumor cell mobilization in leukemia patients, increased circulating leukocytes and decreased platelet counts, splenic enlargement, and fetal harm when given in pregnancy. Adverse reactions that were reported in more than 10% of patients who received plerixafor plus G-CSF and that occurred more often than in patients who received placebo were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting.

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