Palynziq (pegvaliase-pqpz)

POLICY NUMBER

L.5.01.536

Palynziq (pegvaliase-pqpz)

Please perform a formulary drug search on your patient’s Member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific Member’s benefit plan.

DESCRIPTION

Prolonged high blood phenylalanine (Phe) levels are neurotoxic and lead to impairment of intelligence and other brain functions, such as attentiveness. Reduction of blood Phe levels through dietary control is an important determinant of long-term neurologic outcome in phenylketonuria (PKU) patients, and reduction of blood Phe levels in patients with PKU has been shown to decrease the long-term risk of neurologic injury. Pegvaliase is a phenylalanine-metabolizing enzyme that substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations. Palynziq (pegvaliase-pqpz) is indicated to reduce blood Phe concentrations in adult patients with PKU who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. 

Initial Evaluation

Palynziq (pegvaliase-pqpz) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is 18 years of age or older;

2. The individual has a documented diagnosis of Phenylketonuria (PKU) and ALL of the following;

   1. Baseline phenylalanine level >600 micromol/liter on a Phe-restricted diet;

   2. The individual has tried and had an inadequate response to sapropterin (see Policy Guidelines section); AND

   3. The individual is currently on a Phe-restricted diet and will continue along with the requested agent;

3. The requested agent will NOT be used in combination with sapropterin;

4. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g., geneticist);

5. The prescriber agrees to assess patient tolerability, blood Phe concentration, dietary protein, and Phe intake throughout treatment;

6. The prescriber and the individual are both enrolled with the Palynziq REMS Program;

7. Auto-injectable epinephrine has been prescribed and the individual or caregiver instructed in its use;

8. The individual does not have any contraindication(s) to therapy with the requested agent; AND

9. The requested dose is within the FDA-labeled dose range (see Policy Guidelines section).

Length of Approval: 6 months 

Renewal Evaluation Criteria for Approval

Palynziq (pegvaliase-pqpz) may be approved for RENEWAL when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The individual has documented clinical improvement as evidenced by ONE of the following:

   1. ≥20% reduction in blood Phe from pre-treatment baseline; OR

   2. Blood Phe concentration ≤600 micromol/L;

3. The individual is currently on a Phe-restricted diet and will continue diet along with treatment with the requested agent;

4. The requested agent will NOT be used in combination with sapropterin;

5. The prescriber is a specialist or has consulted with a specialist in the area of the individual's diagnosis (e.g., geneticist);

6. Auto-injectable epinephrine has been prescribed and the individual or caregiver instructed in its use;

7. The individual does not have any contraindication(s) to therapy with the requested agent; AND

8. The requested dose is within the FDA-labeled dose range (see Policy Guidelines section).

Length of Approval: 12 months

 Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Kuvan (sapropterin) Trial

Response to Kuvan (sapropterin) therapy is determined by change in blood Phe following treatment at 20mg/kg/day. Treatment should be discontinued in patients who do not show a biochemical response (blood Phe does not decrease) after 1 month of treatment at 20 mg/kg per day.

FDA-Labeled Dosage

^*Additional time may be required prior to each dosage escalation based on patient tolerability.⁺Individualize treatment to the lowest effective and tolerated dosage. Consider increasing to 40 mg once daily in patients who have not achieved a response with 20 mg once daily continuous treatment for at least 24 weeks. Consider increasing to a maximum of 60 mg once daily in patients who have not achieved a response with 40 mg once daily continuous treatment for at least 16 weeks.⁺Discontinue Palynziq (pegvaliase-pqpz) in patients who have not achieved an adequate response after 16 weeks of continuous treatment at the maximum dosage of 60 mg once daily.

• Obtain baseline blood Phe concentration before initiating treatment.

• Assess patient tolerability, blood Phe concentration, and dietary protein and Phe intake throughout treatment.

• Reduce the dosage and/or modify dietary protein and Phe intake, as needed, to maintain blood Phe concentrations within a clinically acceptable range and above 30 micromol/L.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [ie, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

BCBSMS determines patient medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

10/31/2019: New policy added. Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

02/18/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug name to the top of the policy. Policy description updated. Initial and Renewal Evaluation criteria revised. Added statement that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Policy Exceptions updated regarding State Health Plan members. Policy Guidelines updated regarding Kuvan trial, BCBSMS request for medical records, and to define investigative. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Palynziq (pegvaliase-pqpz). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding the individual having a documented diagnosis of Phenylketonuria (PKU), along with meeting all of the listed criteria. Added criteria regarding contraindications to therapy. Renewal criteria updated regarding documented clinical improvement and contraindications to therapy. Policy Guidelines updated regarding Kuvan (sapropterin) therapy. Sources updated.

SOURCE(S)

1. Kuvan prescribing information. BioMarin Pharmaceutical Inc. August 2024. Last accessed April 2025.

2. Palynziq prescribing Information. BioMarin Pharmaceutical Inc. December 2022. Last accessed April 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

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