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FDA Approves Unituxin

FDA Approves Unituxin (dinutuximab) for Pediatric High-Risk Neuroblastoma

On March 10, 2015, the U. S. Food and Drug Administration approved dinutuximab (Unituxin, United Therapeutics Corporation), 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 who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Dinutuximab is a chimeric monoclonal antibody (also known as ch 14.18), composed of a combination of mouse and human DNA.

The approval was based on demonstration of improved event-free survival (EFS) and overall survival (OS) in a multicenter, open-label, randomized trial conducted by the Children’s Oncology Group. Prior to enrollment, patients had achieved at least a partial response to prior therapy for newly diagnosed high-risk neuroblastoma, consisting of induction combination chemotherapy, maximum feasible surgical resection, and myeloablative consolidation chemotherapy, and also received autologous stem cell transplant and radiation therapy.

The trial randomized (1:1) 226 patients to either the dinutuximab/RA arm or the RA alone arm. Patients in each arm received six cycles of treatment. The dinutuximab/RA arm consisted of dinutuximab in combination with GM-CSF and RA (cycles 1, 3, and 5), dinutuximab in combination with IL-2 and RA (cycles 2 and 4), and RA (cycle 6). Patients were 11 months to 15 years of age (median age 3.8 years).

The major efficacy outcome measure was investigator-assessed EFS, defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy, or death. At the seventh interim analysis, an improvement in EFS [HR 0.57 (95% CI: 0.37, 0.89); p = 0.01, log-rank test] was demonstrated and four remaining patients undergoing treatment on the RA arm crossed over to receive dinutuximab/RA. The median EFS was not reached (3.4 years, NR) in the dinutuximab/RA arm and was 1.9 years (1.3, NR) in the RA arm. An analysis of overall survival (OS) conducted three years later documented an improvement in OS in the dinutuximab/RA arm compared to the RA arm [HR 0.58 (95% CI: 0.37, 0.91)]. At the time of this survival analysis, median OS had not been reached in either arm.

Safety data was evaluated in 134 patients. The most common (greater than or equal to 25%) adverse drug reactions in the dinutuximab/RA 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 (greater than or equal to 5%) serious adverse reactions in the dinutuximab/RA group were infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome.

Seventy-one percent of patients in the dinutuximab/RA arm and 77% of patients in the RA alone arm completed planned treatment. The most common reason for premature discontinuation of study therapy was adverse reactions in the dinutuximab/RA group (19%) and progressive disease (17%) in the RA group.

The recommended dose and schedule for dinutuximab is 17.5 mg/m2/day as a diluted intravenous infusion over 10 to 20 hours for 4 consecutive days for up to 5 cycles. Patients require intravenous treatment with opioids prior to, during, and for 2 hours following the dinutuximab infusion to mitigate neuropathic pain. Patients also require prehydration and premedication to decrease the risk of hypotension and serious infusion reactions with dinutuximab.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at:

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Unituxin is a trademark of United Therapeutics Corporation.

Source: U.S. Food and Drug Administration (FDA)

Unituxin (dinutuximab) FDA Approval History

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