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The Food and Drug Administration has approved Blincyto (blinatumomab) for the treatment of patients with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL). Blincyto, made by Amgen, is an immunotherapy that acts a connector between the CD19 protein found on the surface of most B-cell lymphoblasts and the CD3 protein on T-cell lymphocytes.

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"Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. "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."


The drug received the FDA's Breakthrough Therapy designation for this indication earlier this year (OT 8/10/14 issue), and was also subsequently granted Priority Review (OT 11/10/14 issue).


The Breakthrough Therapy designation, enacted as part of the FDA's 2012 Safety and Innovation Act, was created to expedite the development and review time of a potential new drug for serious or life-threatening disease where early clinical evidence suggests the drug may demonstrate substantial improvement compared with existing therapies. The FDA's priority review designation shortens the time to complete a drug's review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA).


The FDA action date for blinatumomab for this indication had been scheduled to be May 19, 2015 at the time the priority review had been granted.


Approximately 6,020 Americans will be diagnosed with ALL and 1,440 will die from the disease in 2014, according to National Cancer Institute estimates. B-cell ALL is a rare form of ALL.


The approval for Blincyto is based on a clinical trial of 185 patients with Philadelphia chromosome-negative relapsed or refractory precursor B-cell ALL to evaluate the drug's safety and effectiveness. All patients were treated with Blincyto infusions for at least four weeks. Thirty-two percent of the patients had complete remission of disease for approximately 6.7 months.


Blincyto is being approved under the FDA's accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing that the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.


The FDA is requiring Amgen to conduct a study to verify that the drug improves survival in participants with relapsed or refractory Philadelphia-negative precursor B-cell ALL.


The drug carries a boxed warning alerting patients and health care professionals that some patients in the clinical trial had problems with low blood pressure and cytokine-release syndrome at the start of the first treatment and experienced a short period of encephalopathy, or other side effects in the nervous system. The most common side effects for patients treated with Blincyto were pyrexia, headache, peripheral edema, febrile neutropenia, nausea, hypokalemia, fatigue, constipation, diarrhea, and tremor.


The FDA approved Blincyto with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks and the potential for preparation and administration errors.