The U.S. Food and Drug Administration (FDA) today granted accelerated approval to blinatumomab (Blincyto) for the treatment of patients with Philadelphia chromosome–negative, relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-cell ALL). Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that activates endogenous T cells when bound to the CD19-expressing target cell.
Precursor B-cell ALL is a rapidly growing type of cancer in which the bone marrow makes too many B-cell lymphoblasts. The Philadelphia chromosome is an abnormality that sometimes occurs in the bone marrow cells of leukemia patients.
Blinatumomab is the first approved drug that engages the body’s T cells to destroy leukemia cells. The drug acts as a connector between the CD19 protein, which is found on the surface of most B-cell lymphoblasts, and CD3, a protein on T-cell lymphocytes. It is intended for patients with relapsed or refractory disease.
“Immunotherapies, especially blinatumomab with its unique mechanism of action, are particularly promising for patients with leukemia,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “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 safety and effectiveness of blinatumomab were evaluated in a clinical study involving 185 adults with Philadelphia chromosome-negative relapsed or refractory precursor B-cell ALL. All participants were treated with blinatumomab for at least 4 weeks via infusion. Results showed 32% of participants achieved complete remission for approximately 6.7 months.
Blinatumomab carries a boxed warning alerting patients and health-care professionals that some clinical trial participants experienced cytokine-release syndrome at the start of the first treatment and encephalopathy or other side effects in the nervous system. The most common side effects seen in blinatumomab-treated participants were pyrexia, headache, peripheral edema, febrile neutropenia, nausea, hypokalemia, fatigue, constipation, diarrhea, and tremor.
The FDA granted blinatumomab Breakthrough Therapy designation, Priority Review, and Orphan Product designation because the sponsor, Amgen, demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; the drug had the potential, at the time the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively. Blinatumomab is being approved more than 5 months ahead of the prescription drug user fee goal date of May 19, 2015, the date the agency was scheduled to complete review of the application.
Blinatumomab 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 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 blinatumomab’s manufacturer to conduct a study to verify that the drug improves survival in participants with relapsed or refractory Philadelphia-negative precursor B-cell ALL.
The FDA approved blinatumomab 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. ■