Regulatory Decision Summary for Palynziq
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?
The purpose of this new drug submission was to seek authorization for the use of Palynziq. After evaluation of the submitted data package, Health Canada authorized Palynziq for the following indication: Palynziq (pegvaliase injection) is indicated to reduce blood phenylalanine concentrations in patients with phenylketonuria (PKU) aged 16 years and older who have inadequate blood phenylalanine control (blood phenylalanine levels greater than 600 micromol/l) despite dietary management.
Why was the decision issued?
Phenylketonuria (PKU) is a rare autosomal recessive disorder in which patients have an abnormal gene for the enzyme phenylalanine hydroxylase (PAH), which is responsible for breaking down the amino acid phenylalanine (Phe). The goal of treatment of PKU is to decrease blood Phe levels to sub-toxic levels. Palynziq contains an enzyme that breaks down Phe, lowering blood Phe levels to target therapeutic levels.
Authorization was based primarily on Phase 3 clinical studies that tested the recommended dose regimen of low-dose induction followed by titration to a stable maintenance dose based on patient response and tolerability. Over the course of the two Phase 3 studies, 261 patients aged 16-55 received treatment for a mean of 32.1 months.
The primary efficacy endpoint was change from baseline in blood Phe level. At drug-naïve baseline, patients had a mean blood Phe level of 1227 micromol/L. Over the course of treatment, 67% of patients that received the induction-titration-maintenance dose regimen achieved blood Phe levels ≤360 micromol/L.
The most frequently reported adverse events in pegvaliase-treated subjects were injection site reactions (93%), arthralgia (86%) and hypersensitivity reactions (>65%), including cutaneous reactions, serum sickness, angioedema, and acute systemic hypersensitivity reactions (i.e. anaphylaxis; 5.6%). Use of pegvaliase during pregnancy and breastfeeding is not recommended.
Risks have been communicated in the recommended product monograph and will continue to be monitored post-market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities, including two observational safety studies.
The recommended dose of Palynziq is a 4-week induction period with dosing of 2.5 mg/week, followed by a structured titration phase with gradual dose escalation to the minimum therapeutic maintenance dose of 20 mg/day. Maintenance dosing of 20-60 mg/day is based on patient response and tolerability. View the Product Mongraph for details.
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
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| PALYNZIQ | 02526263 | BIOMARIN INTERNATIONAL LIMITED | PEGVALIASE 20 MG / ML |
| PALYNZIQ | 02526247 | BIOMARIN INTERNATIONAL LIMITED | PEGVALIASE 2.5 MG / 0.5 ML |
| PALYNZIQ | 02526255 | BIOMARIN INTERNATIONAL LIMITED | PEGVALIASE 10 MG / 0.5 ML |