Regulatory Decision Summary for Aloxi
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.
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What was the purpose of this submission?
This Supplemental New Drug Submission (SNDS) was filed to obtain marketing authorization to expand the indication of Aloxi [palonosetron hydrochloride (HCl)] solution for intravenous (IV) injection for the prevention of chemotherapy induced nausea and vomiting to the pediatric patient population.
Why was the decision issued?
The efficacy and safety of Aloxi in pediatric patients for the treatment of chemotherapy induced nausea and vomiting was based on a single pivotal study. A total of 493 patients (full-analyses set) undergoing highly or moderately emetogenic chemotherapy were randomized (1:1:1) to one of three treatment groups: Aloxi 10 mcg/kg IV (up to 0.75), Aloxi 20 mcg/kg IV (up to 1.50 mg) or ondansetron 0.15 mg/kg given three times (up to a total of 32 mg). Patients underwent up to 4 chemotherapy cycles.
The primary efficacy endpoint was the proportion of patients with a complete response - defined as no vomiting, no retching, and no use of antiemetic rescue medication - from 0 to 24 hours following emetogenic chemotherapy (acute phase) during first cycle. Non-inferiority was only established with Aloxi 20 mcg/kg, which had a lower bound of the confidence interval within the non-inferiority margin of -15.
A key secondary endpoint was complete response from >24 to 120 hours after the administration of chemotherapy (delayed phase). However, statistical and methodological constraints for this assessment resulted in the specification of "acute nausea and vomiting" in the Aloxi indication; effectively, stipulating that efficacy was only definitively established in the day following chemotherapy.
The overall safety profile of Aloxi was comparable with that of the active comparator, ondansetron and not dose-related. Proportions of patients experiencing adverse events were balanced between treatment arms with a profile consistent with a pediatric oncology population undergoing chemotherapy. The most common adverse drug reaction (>1%) was headache.
Significant uncertainties were the limited and heterogeneous pharmacological, efficacy and safety data for patients aged <2 years old. Therefore, the indication was limited to pediatric patients aged 2 to 17 years.
A Risk Management Plan (RMP) was reviewed and found to be acceptable.
The overall benefit-harm-uncertainty profile of Aloxi in pediatric patients was considered positive.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.