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The Food and Drug Administration approved the use of Unituxin (dinutuximab) as part of first-line therapy for use in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA) for the treatment of pediatric patients with high-risk neuroblastoma.

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Unituxin is a chimeric biologic antibody that induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The drug was approved as part of a multimodality regimen that includes surgery, chemotherapy, and radiation therapy for patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy.


"Unituxin marks the first approval for a therapy aimed specifically at the treatment of patients with high-risk neuroblastoma," Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. "Unituxin fulfills a critical need by providing a treatment option that prolongs survival in children with high-risk neuroblastoma."


The drug, made by United Therapeutics, was approved after it had already received priority review and orphan drug designation. Priority review shortens the timeframe for review of drug applications by four months, compared with standard reviews, and is granted to drugs that, if approved, will provide a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan product designation is given to drugs intended to treat rare diseases.


With this approval, the FDA also issued a rare pediatric disease priority review voucher to United Therapeutics, which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. This is the second rare pediatric disease priority review voucher granted by the FDA since the inception of the program, which is designed to encourage development of new therapies for prevention and treatment of certain rare pediatric diseases.


"The FDA approval of dinutuximab represents the culmination of a remarkably productive collaboration between researchers at the NCI-supported Children's Oncology Group, the manufacturing and clinical research groups of NCI, and the oncology team at United Therapeutics," Malcolm Smith, MD, PhD, Associate Branch Chief of Pediatrics in the NCI's Cancer Therapy Evaluation Program, said in a news release from the company.


"Children with neuroblastoma will benefit from this collaboration, and the drug development pathway blazed by dinutuximab will likely be followed in the future to develop other novel agents directed against pediatric cancer therapeutic targets."


The drug's safety and efficacy were evaluated in a clinical trial of 226 pediatric patients with high-risk neuroblastoma whose tumors had shrunk or disappeared after treatment with multiple-drug chemotherapy and surgery followed by additional intensive chemotherapy and who subsequently received bone marrow transplantation support and radiation therapy. Patients were randomly assigned to receive either RA or Unituxin in combination with IL-2 and GM-CSF (which are thought to enhance the activity of Unituxin by stimulating the immune system), and RA.


Three years after treatment, 63 percent of the patients who had received the Unituxin combination were alive and their tumors had not grown or recurred, compared with 46 percent of patients who had received RA alone. And in an updated analysis, 73 percent of patients who had received the Unituxin combination were alive compared with 58 percent of those who had received RA alone.


Boxed Warning

Unituxin carries a Boxed Warning alerting patients and health care professionals that the drug irritates nerve cells, causing severe pain that requires treatment with intravenous narcotics and that can also cause nerve damage and life-threatening infusion reactions, including upper airway swelling, difficulty breathing, and low blood pressure, during or shortly following completion of the infusion.


Unituxin may also cause other serious side effects including infections, eye problems, electrolyte abnormalities, and bone marrow suppression.


The most common side effects of Unituxin were severe pain, fever, low platelet counts, infusion reactions, low blood pressure, hyponatremia, elevated liver enzymes, anemia, vomiting, diarrhea, low potassium levels in the blood, capillary leak syndrome, neutropenia and lymphopenia, hives, and low blood calcium levels.