Regulatory Decision Summary for Unituxin

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):


Therapeutic area:

ATC code: L01XC16

Type of submission:

New Drug Submission

Control number:

What was the purpose of this submission?


This New Drug Submission (NDS) was filed to obtain market authorization for Unituxin (dinutuximab) for the treatment of high-risk neuroblastoma in pediatric patients, when used in combination with cytokines, as part of a multimodality therapy.

After evaluation of the submitted data package, Health Canada (HC) authorized Unituxin for the following indication:

  • Unituxin (dinutuximab) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of high-risk neuroblastoma in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy.


Why was the decision issued?


Authorization was based primarily on the results of a pivotal trial and two supporting trials, all of which enrolled pediatric patients with high-risk neuroblastoma. The pivotal trial was a multicentre, randomized clinical trial comparing the event-free survival (EFS) and overall survival (OS) of pediatric patients who received either Unituxin, GM-CSF, IL-2, and RA (Immunotherapy plus RA) or RA alone after having achieved at least a partial response from prior multiagent, multimodality therapy. The two supporting trials were single-arm studies of patients receiving the same Immunotherapy plus RA. Unituxin is administered by intravenous infusion in all of these studies.

In the pivotal trial, 113 patients were randomized to each treatment. The results showed a statistically significant and clinically meaningful improvement in both the EFS and OS endpoints in favour patients randomized to receive the Immunotherapy plus RA treatment compared to those receiving RA alone. In the supportive single-arm trials, results were comparable to those found in the Immunotherapy plus RA arm of the pivotal trial.

In the pivotal trial, the most common adverse events (AEs) suspected to be study drug-related and reported in at least 20% of patients in the Immunotherapy plus RA arm at the level of ≥ grade 3 severity were lymphopenia, thrombocytopenia, fever, anemia, granulocytopenia, hypokalemia, abdominal pain, drug hypersensitivity, elevated alanine aminotransferase levels, hyponatremia, and capillary leak syndrome (CLS). Furthermore, the types, frequency and severity of AEs associated with the Immunotherapy plus RA arm were similar in the single-arm supportive trials. Only 1 of 4 deaths, not due to disease progression in the Immunotherapy plus RA arm, was attributable to therapy-related causes; the patient died from CLS secondary to an inadvertent overdose of IL-2.

Specific details of required pre-medications to avoid or reduce toxicity, for monitoring, and for managing severe AEs developing after Immunotherapy plus RA therapy are provided in the product monograph (PM). Given the high risk of serious AEs associated with Unituxin-containing therapy, administration of this regimen should be restricted to facilities that are staffed by health care professionals who are well-trained and experienced in managing pediatric patients undergoing this therapy and who have participated in educational programs focusing on the monitoring and management of such AEs.

A Risk Management Plan was submitted and reviewed by MHPD. Educational material for healthcare professionals and patients was also provided by the sponsor.

Balancing the benefits and risks of this Unituxin-containing regimen when given following combination chemotherapy, radiation therapy, and stem cell transplant in this pediatric population with high-risk neuroblastoma, the overall benefit-risk assessment is considered favourable when the regimen is administered in the appropriate clinical setting. The recommended dose of Unituxin for this indication is 17.5 mg/m2/day administered as an intravenous infusion over 10 to 20 hours for each of 4 consecutive days. Further details are available in the PM.

For more information on Health Canadas decision, please view the Summary Basis of Decision.


Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.