Regulatory Decision Summary for Xenpozyme

The purpose of this submission was to seek authorization for a new drug substance, Xenpozyme (olipudase alfa) for the treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD, previously referred to as Niemann-Pick).

After evaluation of the submitted data package, Health Canada authorized Xenpozyme for the long-term treatment of non-central nervous system (CNS) manifestations of acid sphingomyelinase deficiency (ASMD) in pediatric and adult patients.

Authorization in adults was primarily based on 1 randomized, double-blind, placebo-controlled study in adult patients with ASMD Type B. Adult patients (n = 36) with ASMD received either placebo or olipudase alfa (n = 18 each) for 52 weeks, followed by open label treatment of all patients (n = 35) with olipudase alfa in a long-term extension period.

Authorization in pediatric patients was primarily based on 1 open label study in pediatric patients with ASMD Type A/B or B. Pediatric patients aged 12 to <18 years (n = 4), 6 to <12 years (n = 9), or <6 years of age (n = 7) were treated with olipudase alfa for 64 weeks. Patients completing the study were eligible for entry into a separate long-term extension study.

Both adults and pediatric patients were treated with the recommended dose escalation protocol to a target maintenance dose of 3 mg/kg via intravenous infusion every 2 weeks.

In both children and adults, olipudase alfa resulted in a clinically meaningful reduction in spleen and liver volume from baseline. In adult patients and the pediatric patients that were old enough to complete testing, there were substantial improvements in pulmonary function parameters.

The most common adverse reactions (ADRs) reported in at least 10% of patients were headache, pyrexia, urticaria, nausea, vomiting, abdominal pain, myalgia, pruritus, and C-reactive protein increased. Infusion-associated reactions (including hypersensitivity/anaphylaxis) were reported in 55% of adult patients and 65% of pediatric patients.

The recommended dose of the drug is 3 mg/kg via intravenous infusion every 2 weeks, following a 14-week (adults) or 16-week (pediatrics) dose escalation protocol. View the PM for details.

Based on the data evaluated in the new drug submission, Health Canada has determined that the benefit-risk profile for Xenpozyme in pediatric and adult ASMD patients is positive.

An updated Risk Management Plan (RMP) for Xenpozyme was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Xenpozyme has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

A Notice of Compliance was recommended.

For further details about Xenpozyme, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.