DINUTUXIMAB APPROVED FOR HIGH RISK NEUROBLASTOMA

The U.S. Food and Drug Administration has approved dinutuximab (Unituxin) as part of first-line therapy for pediatric patients with high-risk neuroblastoma. Dinutuximab, a chimeric monoclonal antibody that binds to the surface of neuroblastoma cells, is being approved for use as part of a multimodality regimen, including surgery, chemotherapy, and radiation therapy for patients who have achieved at least a partial response to prior first-line multiagent, multimodality therapy.

“Dinutuximab marks the first approval for a therapy aimed specifically for the treatment of patients with high-risk neuroblastoma,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Dinutuximab fulfills a critical need by providing a treatment option that prolongs survival in children with high-risk neuroblastoma.”

The FDA granted dinutuximab priority review and orphan product designation. 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 inception of the program.

Clinical Trial

The safety and efficacy of dinutuximab were evaluated in a clinical trial of 226 pediatric participants with high-risk neuroblastoma whose tumors 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. Participants were randomly assigned to receive either an oral retinoid drug, isotretinoin (13-cis-retinoic acid, or RA), or dinutuximab in combination with interleukin-2 (Proleukin), granulocyte-macrophage colony-stimulating factor, and RA.

Three years after treatment assignment, 63% of participants receiving the dinutuximab combination were alive and free of tumor growth or recurrence, compared to 46% of participants treated with RA alone. In an updated analysis of survival, 73% of participants who received the dinutuximab combination were alive compared with 58% of those receiving RA alone.

Side Effects

The new drug carries a Boxed Warning alerting patients and health-care professionals that dinutuximab irritates nerve cells, causing severe pain that requires treatment with intravenous narcotics, and 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. Dinutuximab may also cause other serious side effects including infections, eye problems, electrolyte abnormalities, and bone marrow suppression.

The most common (≥ 25%) adverse reactions in the dinutuximab group were pain, pyrexia, thrombocytopenia, infusion reactions, hypotension, hyponatremia, increased alanine aminotransferase, anemia, vomiting, diarrhea, hypokalemia, capillary leak syndrome, neutropenia, urticaria, hypoalbuminemia, increased aspartate aminotransferase, and hypocalcemia. The most common (≥ 5%) serious adverse reactions in the dinutuximab group were infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome.