General Information

Palynziq (pegvaliase-pqpz) is a phenylalanine-metabolizing enzyme.

Playnziq is specifically indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.

Palynziq is supplied as a solution for subcutaneous injection. The recommended dosing schedule is as follows:

Induction: The recommended initial induction dosage for Palynziq is 2.5 mg subcutaneously once weekly for 4 weeks. Administer the initial dose under the supervision of a healthcare provider.

Titration: Titrate the Palynziq dosage in a step-wise manner, based on tolerability, over at least 5 weeks, to achieve a dosage of 20 mg subcutaneously once daily. Please see drug label for titration schedule.

Maintenance: Therapeutic response may not be achieved until the patient is titrated to an effective maintenance dosage of Palynziq. Use the lowest effective and tolerated dosage of Palynziq.

Assess patient tolerability, blood phenylalanine concentrations, and dietary protein and phenylalanine intake throughout treatment. Maintain the Palynziq dosage at 20 mg subcutaneously once daily for at least 24 weeks. Consider increasing the Palynziq dosage to a maximum of 40 mg subcutaneously once daily in patients who have been maintained continuously on 20 mg once daily for at least 24 weeks and who have not achieved either a 20% reduction in blood phenylalanine concentration from pre-treatment baseline or a blood phenylalanine concentration less than or equal to 600 micromol/L.

Side Effects

Adverse effects associated with the use of Palynziq may include, but are not limited to, the following:

injection site reactions

arthralgia

hypersensitivity reactions

headache

generalized skin reactions lasting at least 14 days

pruritus

nausea

abdominal pain

oropharyngeal pain

vomiting

cough

diarrhea

fatigue

The Palynziq drug label comes with the following Boxed Warning:

Anaphylaxis has been reported after administration of Palynziq and may occur at any time during treatment. • Administer the initial dose of Palynziq under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer auto-injectable epinephrine, if needed. • Prescribe auto-injectable epinephrine. Prior to first dose, instruct the patient and observer (if applicable) on its appropriate use. Instruct the patient to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during Palynziq treatment.

Clinical Trial Results

The FDA approval of Palynziq was based on the phase III PRISM-2 study. During the double-blind, placebo-controlled, randomized withdrawal period trial (RWP), subjects were randomized in a 2:1 ratio to either continue their maintenance Palynziq dosage (20 mg once daily or 40 mg once daily) or to receive matching placebo for a total of 8 weeks. Palynziq-treated patients maintained their blood Phe concentrations as compared to their randomized withdrawal baseline, whereas patients randomized to matching placebo returned to their pretreatment baseline blood Phe concentrations, which met the primary endpoint of change in blood Phe compared with placebo.