The Food and Drug Administration has approved blinatumomab (Blincyto) for Philadelphia chromosome–negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
The approval on Dec. 3 came almost 5 months early. Blinatumomab maker Amgen applied for accelerated approval with the agency in early October, and a decision was due by May 19, 2015, according to the company.
“Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent,” said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement .
The National Cancer Institute estimates that 6,020 Americans will be diagnosed with ALL and 1,440 will die from the disease in 2014.
The drug is the first bispecific CD19-directed CD3 T-cell engager (BiTE) antibody construct approved by the FDA and is also the first single-agent immunotherapy to be approved for the treatment of patients with Philadelphia chromosome–negative relapsed or refractory B-cell precursor ALL, said Amgen .
The FDA based the approval on results of Amgen’s MT103-211 trial, a phase II, multicenter, single-arm, open-label study. Of the 185 patients evaluated in the trial, 42% (77 of 185) achieved complete remission or complete remission with partial hematologic recovery within two cycles of treatment. Blinatumomab was given by continuous infusion for 4 weeks of a 6-week cycle. Up to two cycles were used for induction and three cycles for consolidation.
The response was durable (with a median of 6.7 months; range, 0.46-16.5 months).
The FDA evaluated safety in 212 patients. The most common adverse reactions were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), and constipation (20%).
Neurologic toxicities – including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders – were common, occurring in almost half of patients, and were a frequent reason for interruption of therapy.
There is a boxed warning on neurologic toxicities and cytokine-release syndrome, which was reported in 11% of the patients. The FDA also is requiring a Risk Evaluation and Mitigation Strategy for blinatumomab, which consists of a communication plan to inform health care providers about the serious risks and the potential for preparation and administration errors.
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