WHA

Palynziq (pegvaliase-pqpz) - PA, NF

Indications for Prior Authorization

Palynziq (pegvaliase-pqpz)
  • For diagnosis of Phenylketonuria (PKU)
    Indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.

Criteria

Palynziq

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s) [A]

  • Diagnosis of phenylketonuria (PKU)
    • AND
  • Patient has uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management (e.g., phenylalanine restricted diet, Kuvan [sapropterin]) [1, B]
    • AND
  • One of the following:
    • Patient has had a trial and failure or intolerance to generic sapropterin
      • OR
    • Patient is not a candidate for generic sapropterin therapy due to the presence of two null mutations in trans [2]
    AND
  • Patient will have phenylalanine blood levels measured every 4 weeks until a maintenance dose is established and periodically thereafter [C]
Palynziq

Prior Authorization (Reauthorization)

Length of Approval: 24 Month(s) [D]

  • Patient has experienced an objective response to therapy, defined by one of the following [A, E]:
    • At least a 20% reduction in blood phenylalanine concentrations from pre-treatment baseline
      • OR
    • Blood phenylalanine concentrations less than or equal to 600 micromol/L
    AND
  • Patient will continue to have phenylalanine blood levels measured periodically during therapy [C]
Palynziq

Non Formulary

Length of Approval: 12 Month(s) [A]

  • Submission of medical records (e.g., chart notes) confirming diagnosis of phenylketonuria (PKU)
    • AND
  • Submission of medical records (e.g., chart notes) confirming patient has uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management (e.g., phenylalanine restricted diet, Kuvan [sapropterin]) [1, B]
    • AND
  • Submission of medical records (e.g., chart notes) or paid claims confirming one of the following:
    • Patient has had a trial and failure or intolerance to generic sapropterin
      • OR
    • Patient is not a candidate for generic sapropterin therapy due to the presence of two null mutations in trans [2]
    AND
  • Patient will have phenylalanine blood levels measured every 4 weeks until a maintenance dose is established and periodically thereafter [C]

  • Guideline ID
    GL-374389

  • Formulary
    Premium

  • Effective date
    Dec 1, 2025

  • P&T approval date
    Aug 16, 2018

P & T Revisions

2025-08-29, 2024-11-04, 2023-10-03, 2023-04-06, 2022-10-31, 2021-10-05

  1. Palynziq prescribing information. BioMarin Pharmaceutical Inc. Novato, CA. November 2020.
  2. Nulmans I, Lequeue S, Desmet L, Neuckermans J, De Kock J. Current state of the treatment landscape of phenylketonuria. Orphanet J Rare Dis. 2025 Jun;20:281.
  3. 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 Jan; 27(1):101289.
  4. Vockley J, Andersson HC, Antshel KM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014 Feb;16(2):188-200.
  1. Palynziq therapy should be discontinued in patients who do not achieve at least a 20% reduction in blood phenylalanine (Phe) concentration from pre-treatment baseline or a blood phenylalanine concentration less than or equal to 600 micromol/L after 16 weeks of continuous treatment with the maximum dosage of 60 mg once daily. Based on the recommended dosing regimen, patients could be evaluated for discontinuation after 65 weeks of therapy. This would allow for induction, titration, maintenance on 20 mg for 24 weeks, 40mg for 16 weeks, and 60 mg for 16 weeks. [1] However, consider discontinuing treatment at any point, at least within 52 weeks, if disease parameters are not achieved. [2]
  2. There is an absolute consensus that treatment should be initiated in all patients with blood Phe levels greater than or equal to 600 micromol/L. [2]
  3. Patients should have blood Phe concentrations measured every 4 weeks after initiation of Palynziq, until a maintenance dosage is established. Periodic monitoring should continue after a maintenance dose is established. [1, 2]
  4. The American College of Medical Genetics and Genomics (ACMG) strongly recommends lifelong treatment for phenylalanine hydroxylase deficiency, such as PKU, in patients whose untreated blood Phe levels were above 360 micromol/L. [3]
  5. The ACMG guideline strongly recommends maintaining Phe less than or equal to 360 micromol/L for life and suggests blood Phe levels should be maintained in the range of 120–360 micromol/L for all patients. Maintaining lifelong Phe levels of 360 micromol/L or lower is associated with higher IQ scores, and achieving Phe levels of 360 micromol/L or lower before conception is substantially associated with lower risks of negative effects to offspring in pregnant patients. [3, 4]
  • 2025-08-29: Annual Review 2025 - Updates to NF criteria to require submission of medical records for diagnosis check & objective measures. Background updates to align with PI (maximum dose of 60 mg) and 2023 ACMG guideline recommendations
  • 2024-11-04: Annual review: No criteria changes.
  • 2023-10-03: Annual review: Updated reauthorization approval length to 24 months.
  • 2023-04-06: update guideline
  • 2022-10-31: 2022 Annual Review - No changes to criteria
  • 2021-10-05: 2021 Annual Review, no changes to criteria.