Phenylketonuria (PKU) Treatments

PALYNZIQ is a clear to slightly opalescent, colorless to pale yellow solution available as follows:

None.

The following serious adverse reactions are discussed below and in other sections of labeling:

Pegvaliase-pqpz is a phenylalanine-metabolizing enzyme that is composed of recombinant phenylalanine ammonia lyase (rAvPAL) conjugated to N-hydroxysuccinimide (NHS)-methoxypolyethylene glycol (PEG). rAvPAL is manufactured in

PALYNZIQ (pegvaliase-pqpz) injection, intended for subcutaneous injection, is a clear to slightly opalescent, colorless to pale yellow, sterile, preservative-free solution and is formulated at pH 6.6 to 7.4.

PALYNZIQ is provided in a single-dose prefilled syringe and is available in three dosage strengths: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/mL. PALYNZIQ contents for each dosage strength are summarized in Table 5.

Study 2 (NCT01819727) was an open-label, randomized, multi-center study of adults with PKU to assess safety and tolerability of self-administered PALYNZIQ in an induction/titration/maintenance regimen with a target maintenance dose of 20 mg subcutaneously once daily or 40 mg subcutaneously once daily. At PALYNZIQ treatment initiation, 253 patients demonstrated inadequate blood phenylalanine control (blood phenylalanine concentration greater than 600 micromol/L) on existing management, and 8 patients had blood phenylalanine concentrations less than or equal to 600 micromol/L. Existing management options included prior or current restriction of dietary protein and phenylalanine intake, and/or prior treatment with sapropterin dihydrochloride. Patients previously treated with sapropterin dihydrochloride were required to discontinue use at least 14 days prior to the first dose.

The 261 enrolled patients were aged 16 to 55 years (mean: 29 years) and had a baseline mean (range) blood phenylalanine of 1,233 (285, 2330) micromol/L. One hundred forty nine out of 261 (57%) patients were taking medical food at baseline and 41 out of 261 patients (16%) were on a Phe-restricted diet at baseline (defined as receiving greater than 75% of total protein intake from medical food). Patients were randomized (1:1) to one of two target maintenance dosage arms: 20 mg once daily or 40 mg once daily. Patients were titrated to reach their randomized target dosage of 20 mg once daily or 40 mg once daily. The duration of titration varied among patients and was based on patient tolerability. Of the 261 enrolled patients, 195 (75%) patients reached their randomized maintenance dosage (103 in the 20 mg once daily arm, 92 in the 40 mg once daily arm). Among the patients who reached their randomized maintenance dosage, patients in the 20 mg once daily randomized arm reached their maintenance dosage at a median time of 10 weeks (range: 9 to 29 weeks) and patients in the 40 mg once daily arm reached their maintenance dosage at a median time of 11 weeks (range: 10 to 33 weeks).

Of the 261 patients who enrolled in Study 2, 54 (21%) patients discontinued treatment during Study 2, 4 patients completed Study 2 and did not continue to Study 3 (referred to as Study 302, NCT01889862), 152 patients continued to the eligibility period of Study 3, and 51 patients continued directly from Study 2 into the long-term treatment period of Study 3.

A total of 164 adult patients with PKU who were previously treated with PALYNZIQ (152 patients from Study 2 and 12 patients from other PALYNZIQ trials) enrolled in Study 3 and continued treatment with PALYNZIQ in Study 3 for up to 13 weeks to assess eligibility for randomized withdrawal period.

Following this period of up to 13 weeks of additional PALYNZIQ treatment in Study 3, eligibility for entry into the efficacy assessment period (randomized withdrawal period) was determined by whether a patient achieved at least a 20% reduction in blood phenylalanine concentration from pre-treatment baseline (when in previous studies). Eighty-six out of 164 patients (52%) met this response target and continued into the randomized withdrawal period. In the double-blind, placebo-controlled, randomized withdrawal period, patients were randomized in a 2:1 ratio to either continue their maintenance PALYNZIQ dosage or to receive matching placebo for a total of 8 weeks. The treatment difference in least squares (LS) mean change in blood phenylalanine concentration from the Study 3 randomized withdrawal baseline to randomized withdrawal Week 8 for each randomized study arm is shown in Table 6. Mean blood phenylalanine concentrations at pre-treatment baseline (Study 2 or other PALYNZIQ trials) are also shown in Table 6. At Study 3 randomized withdrawal Week 8, PALYNZIQ-treated patients (20 mg once daily or 40 mg once daily) maintained their blood phenylalanine concentrations as compared to their randomized withdrawal baseline, whereas patients randomized to matching placebo (20 mg once daily or 40 mg once daily) returned to their pretreatment baseline blood phenylalanine concentrations (Figure 1).

Of 118 patients from Study 2 with a pre-treatment baseline blood phenylalanine concentration greater than 600 micromol/L who were randomized to and received at least one dose of 20 mg once daily PALYNZIQ, 107 patients, 97 patients, 93 patients, 86 patients, and 77 patients were treated for at least 6 months, 12 months, 18 months, 24 months, and 36 months, respectively. During the continuous treatment period, patients were allowed to dose up to 60 mg once daily based on investigator discretion to achieve blood phenylalanine lowering (for example, to achieve blood phenylalanine concentrations between 120 and 360 micromol/L).

Of the 118 patients, a majority (91 patients, 77%) reached their first response, defined as a blood phenylalanine concentration less than or equal to 600 micromol/L, at a time point prior to 36 months. Of the 91 patients, 9 patients (10%) achieved their first response at a dose less than 20 mg once daily, 44 patients (48%) achieved their first response at a dose of 20 mg once daily, 26 patients (29%) achieved their first response at a dose of 40 mg once daily, and 12 patients (13%) achieved their first response at a dose of 60 mg once daily. Of the 44 patients that achieved their first response at a dose of 20 mg once daily, 36 (82%) achieved it by 24 weeks of treatment. Of the 26 patients that achieved their first response at a dose of 40 mg once daily, 18 (69%) achieved it by 16 weeks of treatment. Of the 12 patients that achieved their first response at a dose of 60 mg once daily, 8 (67%) achieved it by 16 weeks of treatment.

Of the 107 patients treated for at least 6 months, 28 (26%), 18 (17%), and 11 (10%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 6 months of treatment. Of the 97 patients treated for at least 12 months, 47 (48%), 41 (42%), and 31 (32%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 12 months of treatment. Of the 93 patients treated for at least 18 months, 64 (69%), 46 (49%), and 36 (39%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 18 months of treatment. Of the 86 patients treated for at least 24 months, 65 (76%), 57 (66%), and 43 (50%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 24 months of treatment. Of the 77 patients treated for at least 36 months, 58 (75%), 51 (66%), and 37 (48%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 36 months of treatment.

Study 4 (NCT05270837) was an open label, randomized, 2-arm study in patients who are 12 to less than 18 years of age who demonstrated inadequate blood phenylalanine control (blood phenylalanine concentration greater than 600 micromol/L) on existing management. Patients were randomized in a 2:1 ratio to receive PALYNZIQ in an induction/titration/maintenance regimen or to continue dietary management for 72 weeks.

Of the 55 randomized patients, 60% were female and 40% were male. The baseline mean (SD) age was 14.4 (1.3) years. The patient population consisted of 87% White, 4% Black, 2% Asian, and 7% not reported. Ethnicity consisted of 4% Hispanic or Latino and 96% not Hispanic or Latino.

Thirty-six patients received PALYNZIQ subcutaneously at doses of 20 mg, 40 mg, or 60 mg per day during maintenance dosing, and 19 patients were included in the diet-only control arm. All patients were required to maintain stable dietary protein intake from medical food and intact food up to week 72. Baseline mean (range) blood phenylalanine was 1,025 (635, 1,555) micromol/L in the PALYNZIQ arm and 1,029 (687, 1414) micromol/L in the diet only arm, respectively. Four patients in the PALYNZIQ arm discontinued from Study 4 up to week 72.

Of the 36 patients enrolled in the PALYNZIQ arm, 34/36 (94%) reached a dose of 20 mg per day (median time to first 20 mg per day dose was 12.1 weeks), 26/36 (72%) reached a dose of 40 mg per day (median time to first 40 mg per day dose was 40 weeks), and 14/36 (39%) reached a dose of 60 mg per day (median time to first 60 mg per day dose was 60.7 weeks).

Patients in the PALYNZIQ arm showed a significant mean reduction from baseline in blood Phe levels at Week 72 compared to patients in the diet only arm (Table 7).

Figure 2 shows the blood phenylalanine concentration over time of patients treated with PALYNZIQ patients on diet only.

PALYNZIQ (pegvaliase-pqpz) injection is supplied as a preservative-free, sterile, clear to slightly opalescent, colorless to pale yellow solution. All dosage strengths of PALYNZIQ are provided in a 1 mL glass syringe with a 26-gauge, 0.5 inch needle.

Each carton contains 1 or 10 trays with single-dose prefilled syringe(s), Prescribing Information, Medication Guide, and Instructions for Use. The following packaging configurations are available.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

PALYNZIQ is available only through a restricted program called the PALYNZIQ REMS

PALYNZIQ is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy

Advise women who are exposed to PALYNZIQ during pregnancy or who become pregnant within one month following the last dose of PALYNZIQ that there is a pregnancy surveillance program that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to BioMarin (1-866-906-6100)

This Instructions for Use contains information on how to inject PALYNZIQ.

Read this Instructions for Use before you start using the PALYNZIQ prefilled syringe and each time you get a new prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Figure B below shows what the prefilled syringe looks like before use.

When you receive your PALYNZIQ prefilled syringe(s), check that the name "Palynziq" appears on the carton(s).

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

U.S. License No. 1649

Revised: 2/2026

NDC 68135-058-90                    

Contains one x 2.5 mg/0.5 mL single-dose prefilled syringe.

Discard after use.

NDC 68135-756-20                    

Contains one x 10 mg/0.5 mL single-dose prefilled syringe.

Discard after use.

NDC 68135-673-40                    

Contains one x 20 mg/mL single-dose prefilled syringe.

Discard after use.

NDC 68135-673-45                    

Contains ten 20 mg/mL single-dose prefilled syringes.

Discard after use.