The US Food and Drug Administration (FDA) has approved vincristine sulfate liposome injection (Marqibo) to treat adults with Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL).
The drug, an injection administered once a week, is approved for patients whose leukemia has relapsed two or more times, or whose leukemia has progressed following two or more regimens of antileukemia therapy (including transplants).
Marqibo utilizes vincristine encapsulated in a rigid, lipid bilayer of sphingomyelin. Vincristine, an FDA-approved, standard chemotherapeutic used in most lymphoma and ALL regimens, is a cell-cycle-specific agent whose activity is dependent on the duration of drug exposure. The sphingosome encapsulated technology employed in the new approved version results in a more rigid liposome that is designed to allow the active vincristine to leak out of the liposome slowly, maintaining drug levels for prolonged periods of time.
“Marqibo’s approval demonstrates the FDA’s commitment to the development and approval of drugs that address serious, unmet medical needs,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a press release. “Marqibo provides an additional option for Philadelphia chromosome–negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies.”
The study that led to the approval, HBS407, was a phase II, international, multicenter, open-label, single-arm clinical trial of 65 heavily pretreated adult patients whose leukemia had relapsed at least two times despite standard treatments, and who had at least one previous treatment response lasting at least 90 days. Response rate to Marqibo was the primary endpoint—either a complete remission or a complete remission with incomplete blood count recovery.
Of the 65 patients enrolled, 10 patients (15.4%) met these endpoints—three patients had a complete remission and seven patients had a complete remission with incomplete blood count recovery. The median duration of documented remission was 28 days, and the median time to the first event of relapse, death, or next therapy was 56 days.
ALL is more commonly diagnosed in children than adults. In 2012, an estimated 6,050 men and women will be diagnosed with ALL and 1,440 will die from the disease, according to the National Cancer Institute. Due to the drug's limited indication, it is estimated that out of the 1,400 adult patients with Philadelphia chromosome–negative ALL, only about 458 a year would be eligible to take it.
Marqibo is marketed by Talon Therapeutics Inc. The accelerated approval of the drug came following a lukewarm recommendation, a 7-to-4 vote, from the Oncologic Drugs Advisory Committee (ODAC). It was the second time that the drug came before the ODAC—the committee unanimously voted against accelerated approval of the agent for aggressive NHL in 2004.
The safety of the vincristine sulfate liposome injection was evaluated in two single-arm trials of 83 patients who received the clinical treatment regimen. Adverse events included fatigue, anemia, hypoesthesia, paresthesia, constipation, peripheral neuropathy, nausea, neutropenia, thrombocytopenia, and abdominal pain. Serious adverse events such as low white blood cell counts with fever, low blood pressure, respiratory distress, and cardiac arrest occurred in 76% of the patients studied.
Marqibo must be administered intravenously, the drug is deadly if administered in other ways, such as into the spinal fluid. The prescribing information will carry a boxed warning alerting patients and health care professionals. To avoid an overdose, the warning also notes that Marqibo has different dosage recommendations than vincristine sulfate injection alone.