The Food and Drug Administration on Aug. 9 approved Marqibo, a liposomal encapsulated version of vincristine, to treat relapsed and refractory Philadelphia chromosome–negative acute lymphoblastic leukemia in adults.
Marqibo was approved for patients who have relapsed twice or more, or whose disease has failed at least two chemotherapy regimens. A nanoparticle formulation of vincristine that allows for dose-intensive treatment, it is manufactured by Talon Therapeutics of South San Francisco, Calif.
Dr. Richard Pazdur
Acute lymphoblastic leukemia (ALL) is diagnosed in about 6,000 adults each year; the Philadelphia chromosome negative type is rare. Talon estimated that about 500 patients a year would be eligible for Marqibo therapy. The FDA designated it as an orphan drug.
"Marqibo provides an additional option for Philadelphia chromosome–negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.
The drug was approved under the agency’s accelerated approval regulations. The FDA said that the data showed that Marqibo had an effect on a surrogate end point – in this case, the response rate – that was likely to predict clinical benefit.
But Marqibo received lukewarm backing from the FDA’s Oncologic Drugs Advisory Committee in late March, in part because the panelists were not impressed with its efficacy.
According to the FDA’s approval statement, of 65 patients enrolled in a phase II study, 10 (15%) had either a complete remission or complete remission with incomplete blood count recovery. The median duration of remission was 28 days. The median time to the first event of relapse, death, or next therapy was 56 days, said the FDA.
The FDA advisers also were concerned about safety, noting that 76% of patients in trials had serious adverse events such as neutropenia, hypotension, respiratory distress, and cardiac arrest. The drug will carry a boxed warning that it should only be administered intravenously because it is deadly if administered in other ways, in particular into the spinal fluid.
The warning states that Marqibo has different dosage recommendations than does vincristine sulfate injection alone. To avoid overdose, drug name and dosing should be verified before administration, said the agency.
Talon said in a statement that the drug should be given at a dose of 2.25 mg/m2 intravenously over 1 hour once every 7 days.
"We are delighted that Marqibo will be available to a patient population with an underserved hematologic malignancy," Dr. Steven R. Deitcher, Talon president and chief executive officer, said in the statement.