Dinutuximab Approved for High-Risk Neuroblastoma

The FDA has approved the use of dinutuximab (Unituxin; United Therapeutics) for high-risk neuroblastoma, offering patients the first major new treatment in more than a decade. Only 30% to 40% of patients, who are typically younger than 5, survive long term with current therapies, but those rates could rise to 45% to 50% with dinutuximab.

The drug is a monoclonal antibody targeting GD2, a glycolipid richly expressed in neuroblastomas that helps promote cell growth. Dinutuximab is approved for patients who have shown some response to first-line therapies such as chemotherapy and surgery and require further treatment to erase any lingering traces of cancer. Until now, the standard treatment at this stage has been isotretinoin, which promotes differentiation of cancer cells.

The approval was based on a phase III clinical trial of 226 patients who had responded at least partially to initial therapies. Half received isotretinoin alone, and the other half received a combination of isotretinoin and dinutuximab, along with interleukin-2 (IL2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to boost their immune response. Three years after treatments were assigned, 63% of dinutuximab patients had survived without disease recurrence, whereas only 46% of patients receiving standard therapy did. Survival rates among all high-risk neuroblastoma patients will be lower because the study did not include patients who fail to respond to initial therapy.

Dinutuximab was approved for use in combination with the drugs in the experimental arm of the trial—isotretinoin, IL2, and GM-CSF.

The approval is significant for patients, says Katherine Matthay, MD, a professor of pediatrics at the University of California, San Francisco, who participated in pilot studies of dinutuximab and helped develop the phase III trial. “It's the first drug ever that was specifically approved to treat neuroblastoma,” she says.

Under an FDA program to encourage development of new therapies for rare pediatric diseases, United Therapeutics received a priority review voucher, which the company can sell or use to hasten the review of another drug application. The FDA has issued only one other such voucher, to BioMarin Pharmaceutical, since the program began in 2012; BioMarin sold its voucher to Regeneron Pharmaceuticals for $67.5 million.

Dinutuximab often causes severe pain during and after the infusion, which can be alleviated with narcotics. Some patients also experience low blood pressure, possibly due to the IL2, and allergic reactions.

Researchers aim to find out whether dinutuximab could be used earlier in treatment. Currently, about 20% of patients do not respond to initial therapies and thus are not eligible for the drug. Alice Yu, MD, PhD, a professor of pediatrics at the University of California, San Diego, who led development of the drug and phase I through III trials, and her colleagues are studying whether dinutuximab in combination with chemotherapy is more effective than chemotherapy alone. Her team also recently completed a pilot study of a vaccine that stimulates a similar immune response against GD2-bearing cells, but with fewer side effects.