ModifiedHealth NetPolicy CP.PHAR.140

Pegvaliase (Palynziq) for phenylketonuria — Coverage Criteria

Defines medical necessity criteria, dosing, and approval durations for pegvaliase (Palynziq) to reduce blood phenylalanine in patients with phenylketonuria (PKU); applies to Health Net lines of business including Commercial, HIM/ICHRA, and Medicaid.

Policy Summary

PayerHealth Net

PolicyPegvaliase (Palynziq) for phenylketonuria — Coverage Criteria

Policy CodePolicy CP.PHAR.140

Change TypePediatric expansioncriteria additions and clarifications

Effective DateDec 1, 2018

Next Review Date

Key ActionSubmit prior authorization with documentation showing diagnosis of PKU, age ≥12, recent Phe >600 µmol/L, prior sapropterin trial (unless contraindicated), adherence to a Phe‑restricted diet, and dosing within limits.

SourceLink

POLICY UPDATE CHANGES

Updated criteria to reflect the newly FDA-approved pediatric use for patients ≥ 12 years of age.

Added adherence to a phenylalanine-restricted diet as an approval requirement.

Added Sephience as an agent that should not be used concurrently with Palynziq.

Differentiated approval duration by line of business: Medicaid/HIM/ICHRA = 12 months; Commercial = 6 months or to member renewal date, whichever is longer.

Brought policy forward to align with the annual review cycle for Kuvan and updated references.

≥ 12minimum covered patient age

>600 µmol/Lrequired Phe for initiation

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Coverage Criteria for Pegvaliase (Palynziq)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial PKU criteria: Member has diagnosis of PKU; prescribed by or in consultation with an endocrinologist, metabolic disease specialist, or genetic disease specialist; age >= 12 years; recent (within 90 days) phenylalanine (Phe) blood level is > 600 µmol/L; member is currently adherent on a phenylalanine-restricted diet and will continue this diet during treatment with Palynziq; failure of generic sapropterin (Kuvan) at up to maximally indicated doses unless contraindicated or intolerant; Palynziq is not prescribed concurrently with sapropterin (Kuvan, Javygtor, Zelvysia) or Sephience; dose does not exceed 20 mg per day.

inv-02: Continuation Therapy

Covered when ALL of the following are met:

Continued PKU criteria: Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; (b) member is currently receiving medication and is enrolled in a state/product with continuity-of-care regulations; member is currently adherent on a phenylalanine-restricted diet and will continue this diet during treatment with Palynziq; Palynziq is not prescribed concurrently with sapropterin (Kuvan, Javygtor, Zelvysia) or Sephience; member meets one of the following for blood Phe control or dose escalation: (a) achieved blood Phe control (blood Phe ≤ 600 µmol/L); (b) request is for 40 mg/day and member has used 20 mg/day continuously for ≥ 6 months without achieving control; (c) request is for 60 mg/day and member has used 40 mg/day continuously for ≥ 16 weeks without achieving control and has not used 60 mg/day continuously for >16 weeks without achieving control; if request is for a dose increase, new dose does not exceed 60 mg per day.

inv-03: Dosing/Administration

Dosing regimen: Initiate 2.5 mg SC once weekly for 4 weeks with the initial dose administered under healthcare provider supervision; titrate in a step-wise manner over ≥ 5 weeks based on tolerability to achieve 20 mg SC once daily; maintain 20 mg SC once daily for ≥ 24 weeks before considering increase to 40 mg once daily; may increase to 60 mg once daily after 40 mg once daily for ≥ 16 weeks if blood Phe remains > 600 µmol/L; maximum dose = 60 mg per day; discontinue if patient has not achieved blood Phe ≤ 600 µmol/L after 16 weeks of continuous treatment at the maximum dosage.

inv-04: Initial and ongoing coverage criteria (updated)

Covered when ALL of the following are met (policy updated):

Age requirement: Patient is ≥ 12 years of age (newly FDA‑approved pediatric use).>=12 years

added per update

Dietary management: Member demonstrates adherence to a phenylalanine-restricted diet and will continue this diet during treatment, as required by the updated criteria.

added per annual review

Non‑FDA indications for Palynziq are not authorized under this clinical policy unless there is sufficient documentation of efficacy and safety per the applicable off‑label use policy or evidence of coverage documents. See the Off‑Label Use Policy references for Commercial (CP.CPA.09), HIM/ICHRA (HIM.PA.154), and Medicaid (CP.PMN.53) when requesting coverage for indications outside the FDA‑approved labeling. Additionally, Palynziq should not be prescribed concurrently with sapropterin products or Sephience, as noted in the exclusions.

For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with this clinical policy. Providers and reviewers should consult the applicable state Medicaid manual or guidance; coverage determinations and exclusions may vary by state and override the provisions described here.

If a patient does not achieve an adequate therapeutic response, continuation of Palynziq is not considered medically necessary. Per the prescribing information, discontinue Palynziq if the patient has not achieved a blood phenylalanine concentration of ≤ 600 µmol/L after 16 weeks of continuous treatment at the maximum recommended dose of 60 mg QD. Documentation of blood Phe results and dosing history is required to support a continuation or discontinuation decision.

This clinical policy is a guide to medical necessity and is intended to assist in coverage decisions and benefit administration. It does not constitute a contract, guarantee of payment, or assurance of coverage. Coverage remains subject to all terms, conditions, exclusions, and limitations of the member's benefit documents and applicable legal and regulatory requirements; the Health Plan may change, amend, or withdraw this policy as needed.

Coding, Clinical Thresholds, and Reference Dates

HCPCS Codes referencedHCPCS

J3590	Unclassified drugs or biologics
C9399	Unclassified drugs or biologics

Internal dates / review referencesmixed

Date = 04.10.26	internal review date/reference
P&T Approval Date = 05.26	pharmacy & therapeutics committee approval date

Blood phenylalanine level for initiation/response — clinical threshold value

Initiation/response threshold> 600 µmol/L (recent Phe within 90 days required)

Monitoring windowRecent blood Phe must be measured within 90 days of request

Response criterion for continuationBlood Phe ≤ 600 µmol/L is considered treatment response

Pediatric age threshold — minimum covered patient age

Minimum covered age≥ 12 years

Basis for changeUpdated to reflect newly FDA‑approved pediatric use for patients ≥ 12 years

Provider Requirements and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must demonstrate that all approval criteria are met before coverage will be authorized. Approval durations differ by line of business: Medicaid/HIM/ICHRA — 12 months; Commercial — 6 months or to the member's renewal date, whichever is longer.

Prior authorization required for Palynziq (pegvaliase‑pqpz).
Approval duration: Medicaid/HIM/ICHRA — 12 months; Commercial — 6 months or to renewal date, whichever is longer.

Prior Authorization

Prior Authorization Aligned to Updated Criteria

PA criteria have been updated to align with the FDA approval for pediatric use. Ensure requests reflect the updated age criterion (patients ≥ 12 years) and include the appropriate line(s) of business (ICHRA may apply).

Updated criteria include pediatric patients aged ≥ 12 years.
ICHRA line of business added to applicability.

Background and Clinical Context

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase (PAH), resulting in elevated blood phenylalanine (Phe) concentrations. Pegvaliase (Palynziq) is a PEGylated phenylalanine ammonia lyase that metabolizes Phe to other products, reducing blood Phe levels and substituting for deficient PAH activity. Treatment with Palynziq requires careful monitoring because of the risk of anaphylaxis (REMS required) and the need for supervised initial dosing. Therapy is intended to lower blood Phe to therapeutic targets; initial approval criteria include a recent blood Phe > 600 µmol/L and age ≥ 12 years, with titration from low weekly doses to a maintenance daily dose and escalation up to a maximum of 60 mg/day per the dosing regimen.

Definitions and Abbreviations

Phe — Phenylalanine abbreviation and definition

AbbreviationPhe

DefinitionPhenylalanine — an amino acid measured in blood for management of phenylketonuria (PKU)

ContextUsed as the laboratory marker to determine initiation, response, and continuation of therapy

PAL — Phenylalanine ammonia lyase enzyme definition

AbbreviationPAL

DefinitionPhenylalanine ammonia lyase — the enzyme class of pegvaliase (Palynziq) that converts phenylalanine to ammonia and trans‑cinnamic acid

Role

Policy Summary

PayerHealth Net

PolicyPegvaliase (Palynziq) for phenylketonuria — Coverage Criteria

Policy CodePolicy CP.PHAR.140

Change TypePediatric expansioncriteria additions and clarifications

Effective DateDec 1, 2018

Next Review Date

SourceLink

On This Page

Denial Risk

Insufficient Documentation May Result in Denial

Prior authorization requests lacking required clinical documentation may be denied. Provider must submit supporting documentation showing all criteria are met.

Required documentation examples: office chart notes, recent lab results (Phe blood level within 90 days), documentation of diagnosis, age, prescriber specialty/consultation.
Requests missing diagnosis, age, recent Phe level, evidence of Phe‑restricted diet adherence, or prescriber specialty may be denied.

Documentation Required

Provider Adherence to Coverage Determinations

Providers must follow coverage determinations as a guide to medical necessity. Coverage decisions are subject to the member's benefit documents, state and federal requirements, and plan administrative policies.

This policy is a guide to medical necessity and not a guarantee of payment.
State Medicaid provisions take precedence when they conflict with this policy.

Step Therapy

Step Therapy Requirement — Sapropterin Failure

Step therapy requirement: failure of generic sapropterin (Kuvan) is required prior to approval unless contraindicated or not tolerated.

Documented trial and failure of sapropterin at up to maximally indicated doses is required, unless contraindication or clinically significant adverse effects are documented.
Palynziq must not be prescribed concurrently with sapropterin (Kuvan, Javygtor, Zelvysia) or Sephience.

Documentation Required

Required Clinical Documentation

Providers must submit specific clinical documentation to support initial and continued therapy criteria. Acceptable documentation includes but is not limited to office chart notes, specialist consultation notes, and laboratory results.

Diagnosis of PKU and documentation of prescriber specialty (endocrinologist, metabolic disease specialist, or genetic disease specialist).
Age documentation confirming ≥ 12 years.
Recent (within 90 days) phenylalanine (Phe) blood level demonstrating > 600 µmol/L for initial approval, or documentation of Phe control for continuation criteria (≤ 600 µmol/L as applicable).
Evidence of adherence to a phenylalanine‑restricted diet and plan to continue the diet during treatment.
Documentation of prior sapropterin trial details (dose, duration, reason for failure or intolerance) if applicable.
For dose increases, documentation supporting prior dosing history and duration per continuation criteria.

Note

Medicaid Precedence for Provider Actions

If state Medicaid coverage provisions conflict with this clinical policy, state Medicaid requirements take precedence and may impose different documentation or authorization requirements.

Refer to the state Medicaid manual for state‑specific coverage provisions.
When applicable, follow state Medicaid addendums and continuity of care regulations referenced in plan materials.