Commercial Pediatric Cancer Immunotherapy, Dinutuximab, Found Equal to Trial Formulation

Commercial Pediatric Cancer Immunotherapy, Dinutuximab, Found Equal to Trial Formulation

Children’s Hospital Los Angeles (CHLA) researchers, building on more than  20 years of work into an immunotherapy, dinutuximab, approved as a treatment for pediatric neuroblastoma, have shown that its commercially manufactured form is equivalent to that used in pivotal clinical trials. The study supported the use of Unituxin (dinutuximab) — the first U.S. Food and Drug Administration (FDA)-approved pediatric immunotherapy — as manufactured by United Therapeutics.

It also argued that the formulation created by the National Cancer Institute (NCI) for the pivotal studies should be made commercially available, precisely because of its equivalence to the FDA-approved therapy.

Titled “Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy” and published in the journal Cancer Chemotherapy and Pharmacology,  the study’s objective was to compare the pharmacokinetics of  Unituxin to NCI dinutuximab, and to test its safety and tolerability.

“After a two-year study that compared commercially manufactured dinutuximab to the material produced by NCI, we see no difference in how patients metabolize or respond to the treatment,” said Araz Marachelian, MD, principal investigator at CHLA. “I, along with my colleagues across the country, are proud of the work that has been done to make additional therapies available for children with this devastating disease.”

Dr. Marachelian, an assistant professor of clinical pediatrics at the Keck School of Medicine of at the University of Southern California, Los Angeles, and director of the New Approaches to  Neuroblastoma Therapy (NANT) consortium, is currently  leading two trials investigating the use of dinutuximab in combination with other agents.

Dinutuximab was developed to harness a patient’s own immune system to fight neuroblastoma, a type of cancer that affects the nervous system surrounding the brain and tends to occur in children starting at age 5. Even though aggressive treatments are available, a number of these children fail to respond to therapy or experience cancer recurrence.

The Children’s Oncology Group led a randomized, Phase 3 trial testing the pharmacokinetic comparability, safety, and tolerability of the United Therapeutics and NCI forms of dinutuximab in 28 children, age 8 or younger, with high-risk neuroblastoma. The researchers reported comparable equivalence between the two forms in terms of pharmacokinetic parameters, systemic exposures, and adverse events, with “no notable safety or tolerability differences.” In the clinical trials that led to the treatment’s FDA approval, dinutuximab was determined to improve patients’ event-free survival and overall survival in comparison to those not receiving the monoclonal antibody as immunotherapy.

Unituxin (dinutuximab) by United Therapeutics was approved by the FDA in March 2015 as part of a first-line therapy for pediatric patients with high-risk neuroblastoma, a common cancer in young children. The therapeutic’s use for this patient group also received marketing approval from the European Commission in August 2015.