The Food and Drug Adminis-tration has approved the use of the orphan drug Marqibo (vincristine sulfate liposome injection) to treat adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). The approval, made under the FDA's accelerated approval program, is for patients who have had disease relapse two or more times, or whose leukemia has progressed following two or more regimens of anti-leukemia therapy.
“Marqibo's approval demonstrates the FDA's commitment to the development and approval of drugs that address serious, unmet medical needs,” Richard Pazdur, MD, the FDA's Director of the Office of Hematology and Oncology Products, said in a statement. “Marqibo provides an additional option for Philadelphia chromosome negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies.”
The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. The program provides earlier patient access to promising new drugs while the company conducts additional clinical studies to confirm the drug's clinical benefit and safe use. Marqibo had earlier received an Orphan Drug designation by the FDA because it is intended to treat a rare disease or condition.
The effectiveness of Marqibo, marketed by Talon Therapeutics Inc., was evaluated in a single clinical trial in 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. Of 65 patients enrolled, 10 (15%) responded with either a complete response (CR) or a complete response with “incomplete blood count recovery (CRi). In the 10 patients achieving CR or CRi, the median duration of documented remission was 28 days. The median time to the first event of relapse, death, or next therapy was 56 days.
The drug's safety was evaluated in two single-arm trials of 83 patients who received the clinical treatment regimen. Serious adverse events such as low white blood cell counts with fever, low blood pressure, respiratory distress, and cardiac arrest occurred in 76 percent of the patients studied. The most common side effects observed during clinical studies were constipation, nausea, low blood cell counts, fever, nerve damage, fatigue, diarrhea, decreased appetite, and insomnia.
Prescribing information will carry a Boxed Warning alerting patients and health care professionals that the drug must be administered only intravenously because “it is deadly if administered in other ways, such as into the spinal fluid.” The Boxed Warning also states that Marqibo has different dosage recommendations than vincristine sulfate injection alone. To avoid overdose, it is important for health care professionals to verify the drug name and the dose before administration, the FDA cautioned, and detailed specific special requirements for preparation of the drug are included on the label.