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BH4 THERAPIES AND
RESTRICTED DIETS
MAY NOT BE THE RIGHT CHOICE FOR MANY PEOPLE WITH PKU1-4

Restricted diets are challenging1,2

BH4 therapies are not always an option3,4

PKU management that requires a restricted diet is often ineffective1,2

Dietary adherence becomes especially challenging as children reach adolescence and face:

When dietary adherence is lost early, it can be hard to regain later10,11

When dietary adherence is lost it's hard to regain

PKU management decisions made during adolescence can set the tone for long-term Phe control.6,10,14

BH4 therapies are not an option for some people with classical PKU3,4

  • BH4 therapies rely on some PAH activity, which is minimal or absent in people with classical PKU4,15
  • The requirement of a long-term restricted diet will continue to present challenges4

Patients need flexibility to meet their PKU treatment goals.

Explore PALYNZIQ trials

 

BH4, tetrahydrobiopterin; PAH, phenylalanine hydroxylase enzyme.


References: 1. Enns GM, Koch R, Brumm V, Blakely E, Suter R, Jurecki E. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab. 2010;101(2-3):99-109. doi:10.1016/j.ymgme.2010.05.017 2. Ashe K, Kelso W, Farrand S, et al. Psychiatric and cognitive aspects of phenylketonuria: the limitations of diet and promise of new treatments. Front Psychiatry. 2019;10:561. doi:10.3389/fpsyt.2019.00561 3. Rocha JC, Ahring KK, Bausell H, et al. Expert consensus on the long-term effectiveness of medical nutrition therapy and its impact on the outcomes of adults with phenylketonuria. Nutrients. 2023;15(18):3940. doi:10.3390/nu15183940 4. Spécola N, Chiesa A. Alternative therapies for PKU. J Inborn Errors Metab Screening. 2017;5:1-5. doi:10.1177/2326409816685734 5. Smith WE, Berry SA, Bloom K, et al. Phenylalanine hydroxylase deficiency diagnosis and management: a 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025;27(1):101289. doi:10.1016/j.gim.2024.101289 6. Burton BK, Hermida Á, Bélanger-Quintana A, et al. Management of early treated adolescents and young adults with phenylketonuria: development of international consensus recommendations using a modified delphi approach. Mol Genet Metab. 2022;137(1-2):114-126. doi:10.1016/j.ymgme.2022.07.012 7. Remor E, Gabe KM, Teruya KI, Schwartz IVD. What is known about patients’ quality of life with phenylketonuria and their caregivers? A scoping review. Orphanet J Rare Dis. 2024;19(1):402. doi:10.1186/s13023-024-03422-4 8. Cazzorla C, Gaiga G, Medici S, et al. Transitioning into adulthood with PKU: the role of diet, coping strategies, and quality of life in adolescents and young adults. Psychol Int. 2025;7(2):45. doi:10.3390/psycholint7020045 9. Pinto A, Daly A, Evans S, Ashmore C, MacDonald A. Navigating adolescence with PKU: adherence, metabolic control, and wellbeing in a UK clinical centre. Nutrients. 2025;17(21):3409. doi:10.3390/nu17213409 10. Beghini M, Pichler M, Tinnefeld FC, et al. Poor adherence during adolescence is a risk factor for becoming lost to follow-up in patients with phenylketonuria. Mol Genet Metab Rep. 2024;39:101087. doi:10.1016/j.ymgmr.2024.101087 11. Ford S, O’Driscoll M, MacDonald A. Living with phenylketonuria: lessons from the PKU community. Mol Genet Metab Rep. 2018;17:57-63. doi:10.1016/j.ymgmr.2018.10.002 12. Cazzorla C, Bensi G, Biasucci G. Living with phenylketonuria in adulthood: the PKU ATTITUDE study. Mol Genet Metab Rep. 2018;16:39-45. doi:10.1016/j.ymgmr.2018.06.007 13. Anton-Paduraru DT, Trofin F, Chis A. Current insights into nutritional management of phenylketonuria: an update for children and adolescents. Children. 2025;12(2):199. doi:10.3390/children12020199 14. Romani C, Manti F, Nardecchia F, et al. Adult cognitive outcomes in phenylketonuria: explaining causes of variability beyond average Phe levels. Orphanet J Rare Dis. 2019;14(1):273. doi:10.1186/s13023-019-1225-z 15. Blau N, Hennermann JB, Langenbeck U, Lichter-Konecki U. Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies. Mol Genet Metab. 2011;104(suppl):S2-S9. doi:10.1016/j.ymgme.2011.08.017

IMPORTANT SAFETY INFORMATION

BOXED WARNING: ANAPHYLAXIS

 

  • 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’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and to administer epinephrine, if needed
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use
  • Prescribe epinephrine for all patients treated with PALYNZIQ. Prior to the 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 epinephrine with them at all times during PALYNZIQ treatment
  • PALYNZIQ is available only through a restricted program called PALYNZIQ REMS (Risk Evaluation and Mitigation Strategy). Further information, including a list of qualified pharmacies, is available at PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367)

WARNINGS AND PRECAUTIONS

Anaphylaxis

  • Signs and symptoms of anaphylaxis reported include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat swelling or tightness, flushed or red skin, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea)
  • Anaphylaxis generally occurred within 1 hour after injection; however, delayed episodes occurred up to 48 hours after PALYNZIQ administration
  • Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose.
  • In clinical trials of primarily adult patients with an induction/titration/maintenance dosage regimen, 29/285 (10%) experienced a total of 42 anaphylaxis episodes.
  • In a clinical trial of patients 12 to less than 18 years of age, 4/36 (11%) of PALYNZIQ-treated patients experienced 1 episode of anaphylaxis.

Other Hypersensitivity Reactions

  • Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgment of the healthcare provider.
  • In clinical trials of primarily adult patients taking PALYNZIQ, hypersensitivity reactions, other than anaphylaxis, were reported in 204/285 (72%) of patients. In a clinical trial of patients 12 to less than 18 years old taking PALYNZIQ, these reactions were reported in 12 out of 36 (33%) of patients.

Injection Site Infections

  • Serious injection site infections including abscess, cellulitis, necrosis, and ulcer have been reported. Some cases required hospitalization, surgical debridement, intravenous antibiotics, and discontinuation of PALYNZIQ
  • Provide proper training to patients and/or caregivers on the use of aseptic injection technique, injection site rotation and to check the site for redness, swelling, or tenderness. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen.

Hypophenylalaninemia (HypoPhe)

Some patients have experienced HypoPhe; monitor blood Phe levels periodically during treatment. Frequent blood Phe monitoring is recommended in the pediatric population. For blood Phe concentrations below 30 micromol/L, the dosage of PALYNZIQ may be reduced and/or dietary protein and Phe intake may be modified to maintain blood Phe concentrations within a clinically acceptable range and above 30 micromol/L.

ADVERSE REACTIONS

The most common adverse reactions in clinical trials of primarily adult patients (at least 20% in either treatment phase) were injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety.

  • Arthralgia: In clinical trials, 245 out of 285 (86%) primarily adult patients experienced episodes consistent with arthralgia (includes back pain, musculoskeletal pain, pain in extremity, and neck pain).
  • Injection site reactions were reported as early as after the first dose of PALYNZIQ and occurred at any time during treatment.
  • Generalized Skin Reactions: In clinical trials, 134 out of 285 (47%) primarily adult patients treated with PALYNZIQ experienced generalized skin reactions (not limited to the injection site) lasting at least 14 days.
  • Angioedema and serum sickness: In clinical trials, 22 out of 285 (8%) primarily adult patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema, and face edema) occurring independent of anaphylaxis. In clinical trials, serum sickness was reported in 7 out of 285 (2%) primarily adult patients.

In the clinical trials, adverse reactions were associated with treatment discontinuation, dosage reduction and temporary drug interruption. In the 285 primarily adult patients exposed to PALYNZIQ in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions.

Pediatric Patients: In a clinical study of 55 patients aged 12 to less than 18 years of age, the most common adverse reactions (at least 20% and greater than in control) were injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. Two patients (5.6%) discontinued treatment due to adverse reactions.

Blood Phenylalanine Monitoring and Diet

  • Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. Periodically monitor blood Phe concentrations during maintenance therapy
  • Counsel patients to monitor dietary protein and Phe intake, and adjust as directed by their healthcare provider

DRUG INTERACTIONS

Effect of PALYNZIQ on Other PEGylated Products

  • In a single-dose study of PALYNZIQ in adult patients with PKU, two patients receiving concomitant injections of medroxyprogesterone acetate suspension (a formulation containing PEG 3350) experienced a hypersensitivity reaction. One of the two patients experienced anaphylaxis
  • The clinical effects of concomitant treatment with different PEGylated products are unknown. Monitor patients treated with PALYNZIQ and concomitantly with other PEGylated products for hypersensitivity reactions including anaphylaxis

USE IN SPECIFIC POPULATIONS

Pregnancy and Lactation

Available data do not establish an increased risk of adverse developmental outcomes to the fetus exposed to PALYNZIQ.

  • 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. Healthcare providers should report PALYNZIQ exposure and encourage these patients to report their pregnancy to BioMarin (1-866-906-6100)
  • Monitor blood Phe levels in breastfeeding women treated with PALYNZIQ to ensure maintenance of blood Phe <360 micromol/L. Adjust dosage and/or dietary protein and Phe intake as needed to avoid concentrations below 30 micromol/L

Pediatric & Geriatric Use: The safety and effectiveness of PALYNZIQ in pediatric patients from birth to less than 12 years have not been established. Clinical studies of PALYNZIQ did not include patients aged 65 years and older.

You are encouraged to report suspected adverse reactions to BioMarin at 1-866-906-6100, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


Please see full Prescribing Information, including BOXED WARNING, and the Medication Guide.

INDICATION

PALYNZIQ® (pegvaliase-pqpz) is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood Phe concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood Phe concentrations greater than 600 micromol/L (10 mg/dL) on existing management.