PALYNZIQ

What it is

PALYNZIQ contains pegvaliase, a covalent conjugate of the protein phenylalanine ammonia lyase (rAvPAL) with NHS-methoxypolyethylene glycol (NHS-PEG). It is presented as a solution for injection. Three strengths are registered on the ARTG: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/1 mL, all as pre-filled syringes.

Approved indications

— Treatment of patients with phenylketonuria (PKU) aged 16 years and older who have inadequate blood phenylalanine control despite prior management with available treatment options.

Dosing overview

The recommended starting dose is 2.5 mg administered once per week for 4 weeks. The dose is escalated gradually based on tolerability to achieve blood phenylalanine levels of 120 to 600 micromol/L. The maintenance dose is individualised to achieve blood phenylalanine control between 120 to 600 micromol/L, taking into account patient tolerability and dietary protein intake. Maintenance dosing options range from 20 mg daily up to a maximum recommended dose of 60 mg daily (administered as three consecutive 20 mg injections). PALYNZIQ is administered by subcutaneous injection.

Key safety warnings

Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with PALYNZIQ and can occur at any time during treatment. The risk of hypersensitivity reactions is 2.6-fold higher in the induction/titration phase compared to the maintenance phase, and the risk of acute systemic hypersensitivity reactions is 6-fold higher in induction/titration phase. Premedication prior to each dose is required during induction and titration with an H1-receptor antagonist, H2-receptor antagonist, and antipyretic. Initial injections should be administered under healthcare professional supervision with 60-minute observation, and patients must be trained on signs and symptoms of hypersensitivity reactions and carry an adrenaline injection device at all times during treatment. Serious injection site infections including abscess, cellulitis, necrosis, and ulcer have been reported, with some cases requiring hospitalisation, surgical debridement, intravenous antibiotics, and discontinuation of PALYNZIQ. Patients and caregivers should receive proper training on aseptic injection technique and rotate injection sites with each dose. In clinical trials, 46% of patients developed hypophenylalaninaemia (blood phenylalanine levels below 30 micromol/L), with the risk 2.1-fold higher in the maintenance phase. The long-term clinical consequences of chronic hypophenylalaninaemia are unknown, and based on animal studies, hypophenylalaninaemia in pregnant women with PKU treated with PALYNZIQ may be associated with adverse fetal outcomes.

Contraindications

PALYNZIQ is contraindicated in patients with severe systemic hypersensitivity reaction or recurrence of a mild to moderate acute systemic hypersensitivity reaction to pegvaliase, any of the excipients, or another PEGylated medicinal product.

PBS listing

PALYNZIQ is not listed on the Pharmaceutical Benefits Scheme. The PBAC recommended against listing in July 2022 for phenylketonuria in patients aged 16 years and over who are not responsive to sapropterin.

Regulatory history

The TGA approved PALYNZIQ on 6 July 2021 for the treatment of patients aged 16 years and older with phenylketonuria who have inadequate blood phenylalanine control despite prior management. PALYNZIQ was listed on the ARTG on 14 July 2021 in three strengths (2.5 mg, 10 mg, and 20 mg). The approval was based on a critical review of evaluation reports from the European Medicines Agency via the COR-B process.