First FDA Approval: Combination Therapy for Rare Childhood Cancer, Neuroblastoma

On March 10, 2015, the Food and Drug Administration (FDA) approved Unituxin™ (dinutuximab) as part of first-line therapy for pediatric patients with high-risk neuroblastoma, a rare cancer that most often occurs in young children. This approval was the result of a collaborative effort between the National Cancer Institute (NCI), the Children’s Oncology Group, and United Therapeutics Corporation (UTC) for the first approved therapy for pediatric high-risk neuroblastoma. Dinutuximab (or monoclonal antibody ch14.18) binds to a ganglioside commonly expressed on the surface of neuroblastoma tumor cells. This binding triggers an immune response that kills the cancer cells.

The NCI Technology Transfer Center (TTC) played an important role in this discovery-to-commercialization story — from its concerted efforts to find and identify a partner strongly committed to moving this important treatment through commercialization and FDA licensure processes to negotiation of a Cooperative Research and Development Agreement (CRADA), and several other technology transfer agreements necessary to support this commercialization effort.

NCI’s Biopharmaceutical Development Program (BDP) played an instrumental role in supporting this project over the years. Specifically, ch14.18 was produced under NCI contracts/subcontracts and provided for NCIfunded clinical studies through the BDP. The BDP worked directly with NCI, the FDA, and Health Canada on issues of patient safety and product characterization. NCI BDP’s Regulatory Affairs group worked extensively with NCI’s Cancer Therapy Evaluation Program (CTEP), the FDA, and Health Canada to develop regulatory submissions and ensure their submission in a timely manner.

A CRADA allowed the transfer of NCI BDP’s evolving drug production process to UTC, the company that would take the product to licensure. The agreement also supported data transfer from NCI’s Division of Cancer Treatment and Diagnosis clinical trials to UTC needed for FDA approval of ch14.18 as a treatment in children with high-risk neuroblastoma.

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.

Awardees:

NIH - National Cancer Institute:

• Donna Bialozor
• Dr. Malcolm Smith
• Dr. Karen Muszynski
• Dr. Jan Casadei
• Dr. Sherry Ansher

United Therapeutics Corporation:

• Dr. L. Mary Smith

Leidos Biomedical Research, Inc.:

• Beverly Keseling