ModifiedCentenePolicy CP.PHAR.140

Pegvaliase-pqpz (Palynziq)

Clinical coverage criteria and prior authorization requirements for pegvaliase-pqpz (Palynziq) to reduce blood phenylalanine in patients with phenylketonuria (PKU); applies to Centene lines of business including Commercial, HIM/ICHRA, and Medicaid.

Policy Summary

PayerCentene

PolicyPegvaliase-pqpz (Palynziq)

Policy CodePolicy CP.PHAR.140

Change TypeCriteria revised (pediatric indication addeddiet adherence and agent restrictions updated)

Effective DateDec 1, 2018

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, age (≥12), recent Phe >600 µmol/L, diet adherence, prior sapropterin failure, and prescriber specialty.

SourceLink

POLICY UPDATE CHANGES

Updated criteria to reflect the newly FDA-approved pediatric use for patients ≥ 12 years of age and added ICHRA line of business.

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

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

Updated to align with the annual review cycle for Kuvan and added adherence to a Phe-restricted diet per plan feedback.

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

Added ICHRA line of business.

≥12minimum covered age

>600 µmol/Lrequired Phe for initiation

20 mg/day

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60 mg/dayabsolute maximum dose

6 mo (Comm) / 12 mo (Med)approval duration

2Q 2026annual review

Coverage Criteria for Pegvaliase (Palynziq)

inv-01: Initial Therapy

Covered when ALL of the following are met:

Initial Approval for PKU: 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) blood phenylalanine (Phe) level is > 600 µmol/L; member is currently adherent to 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 clinically significant adverse effects are experienced; Palynziq is not prescribed concurrently with sapropterin (Kuvan, Javygtor, Zelvysia) or Sephience; dose does not exceed 20 mg per day.

inv-02: Continuation Therapy

Continued therapy is covered when ALL of the following are met:

Continued Therapy for PKU: Member currently receiving medication via Centene benefit or member previously met initial approval criteria (or continuity of care applies); member is currently adherent to 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: (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 blood Phe control; (c) request is for 60 mg/day and member has previously used 40 mg/day continuously for ≥ 16 weeks without achieving blood Phe 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: Other Indications

Other uses

Other Diagnoses/Indications: If this drug has had a recent label change (within the last 6 months) not yet reflected in this policy, follow the referenced no-coverage or non-formulary policies for the applicable line of business; otherwise, if the requested use (diagnosis, age, dosing) is not listed under 'Diagnoses/Indications for which coverage is NOT authorized' and the label-change pathway does not apply, refer to the off-label use policy for the relevant line of business (CP.CPA.09, HIM.PA.154, or CP.PMN.53).

inv-04: Updated Coverage Criteria Highlights

Policy criteria revised — see full policy for complete medical necessity logic.

Pediatric approval: Patient meets FDA‑approved age (≥ 12 years)age >= 12 years

Added per RT4 update

Diet adherence: Documentation of adherence to a phenylalanine‑restricted diet is requiredN/A

Added to align with plan feedback and Sephience criteria

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety consistent with the applicable off‑label use policy for the member’s line of business: CP.CPA.09 (Commercial), HIM.PA.154 (ICHRA/Marketplace), or CP.PMN.53 (Medicaid), or where an evidence of coverage document permits the use.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers and reviewers should consult the relevant state Medicaid manual for any specific coverage rules that apply to Medicaid members.

Use of pegvaliase (Palynziq) for indications that are not FDA‑approved and are not addressed in this policy is considered not authorized (not medically necessary) unless the request meets the documentation and evidentiary requirements described in the applicable off‑label use policy referenced above.

Coding and Clinical Metrics

HCPCS Codes referencedHCPCS

J3590	Unclassified drugs or biologics
C9399	Unclassified drugs or biologics

Affected Codesmixed

affected codes

placeholder for procedure/drug codes impacted by prior authorization updates

inv-10: Blood phenylalanine (Phe) level — initiation and response thresholds

Initiation blood Phe threshold> 600 µmol/L (recent within 90 days required for initial approval)

Response / control goalBlood Phe ≤ 600 µmol/L (used to determine continued therapy or adequate response)

Monitoring timeframe for initial levelRecent blood Phe must be within 90 days of request

Dose‑response criteria related to Phe controlEscalation decisions (20 → 40 → 60 mg/day) tied to failure to achieve blood Phe ≤ 600 µmol/L per specified treatment durations

inv-11: Age — minimum covered age

Minimum covered age≥ 12 years

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Palynziq (pegvaliase-pqpz). Coverage is authorized only when all clinical criteria in the policy are met and supporting documentation is submitted.

Prior authorization required
Approval contingent on meeting all policy criteria

Documentation Required

Documentation Required for Review

Provider must submit documentation (such as office chart notes, laboratory results, Phe blood levels, previous medication records, and any specialist consultation notes) to support that the member meets all approval criteria.

Office notes and lab results (including recent Phe within 90 days)
Documentation of phenylalanine-restricted diet adherence

Background and Clinical Rationale

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficient phenylalanine hydroxylase (PAH) activity, resulting in elevated blood phenylalanine (Phe) concentrations. Pegvaliase‑pqpz (Palynziq) is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine into downstream metabolites, thereby lowering blood Phe levels. Therapy with pegvaliase carries a risk of hypersensitivity reactions, including anaphylaxis, and requires enrollment in the manufacturer's REMS program; prescribers should consider these safety requirements when evaluating candidates for treatment.

Definitions and Terms

inv-22: phenylalanine ammonia lyase (PAL) definition

DefinitionPhenylalanine ammonia lyase (PAL) is an enzyme formulation (pegvaliase) that converts phenylalanine to ammonia and trans‑cinnamic acid, substituting for deficient PAH activity in PKU.

Clinical rolePAL (pegvaliase‑pqpz / Palynziq) reduces blood phenylalanine concentrations in patients with PKU.

Safety noteTherapy with pegvaliase carries risk of anaphylaxis and requires REMS enrollment (see policy safety info).

inv-23: phenylalanine (Phe) definition

DefinitionPhenylalanine (Phe) is the amino acid measured in blood; elevated Phe defines phenylketonuria (PKU).

Use in policyBlood Phe concentration thresholds (e.g., >600 µmol/L initiation, ≤600 µmol/L response) drive coverage decisions for pegvaliase.

Policy Summary

PayerCentene

PolicyPegvaliase-pqpz (Palynziq)

Policy CodePolicy CP.PHAR.140

Change TypeCriteria revised (pediatric indication addeddiet adherence and agent restrictions updated)

Effective DateDec 1, 2018

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, age (≥12), recent Phe >600 µmol/L, diet adherence, prior sapropterin failure, and prescriber specialty.

SourceLink

On This Page

Pediatric update noteCriteria revised to reflect newly FDA‑approved pediatric use for patients ≥ 12 years of age

Documentation expectationProviders should document patient age to demonstrate FDA‑approved indication

inv-12: Dose limits — initial target and maximum dosing details

Initial target dosingTitrate to and maintain 20 mg SC once daily (target) after initiation and titration period

Stepwise escalation criteriaConsider increasing to 40 mg QD after ≥ 24 weeks on 20 mg QD without achieving blood Phe ≤ 600 µmol/L

Maximum dose for continued therapyMay increase to a maximum of 60 mg QD for patients on 40 mg QD ≥ 16 weeks without control; new dose must not exceed 60 mg/day

Titration and duration specificsInitiate 2.5 mg SC weekly x4, titrate over ≥ 5 weeks to 20 mg QD; maintain 20 mg QD ≥ 24 weeks before considering 40 mg QD; 40 mg QD ≥ 16 weeks before considering 60 mg QD

Records showing prior sapropterin (Kuvan) trial or documentation of contraindication/adverse effects

Denial Risk

Denial Risk: Insufficient or Non‑Compliant Documentation

Failure to provide the required supporting documentation or requests for non‑FDA‑approved indications without applicable off‑label policy support may result in denial of the prior authorization.

Lack of required supporting documentation may trigger denial
Off‑label use requires adherence to applicable off‑label policies (see CP.CPA.09, HIM.PA.154, CP.PMN.53)

Step Therapy

Step‑Therapy Requirement: Sapropterin (Kuvan) Trial

For initial approval, member must have failed generic sapropterin (Kuvan) at up to maximally indicated doses unless sapropterin is contraindicated or the member experienced clinically significant adverse effects. Provide documentation of sapropterin trial (dose, duration, response) or documentation of contraindication/adverse reaction.

Evidence of trial of sapropterin (Kuvan/Javygtor/Zelvysia) at maximally indicated doses
If no trial, documentation of contraindication or clinically significant adverse effects

Documentation Required

Updated Documentation Expectations (including pediatric use ≥ 12 years)

Documentation expectations have been updated to reflect FDA pediatric approval for use in patients ≥ 12 years and to require documentation of adherence to a phenylalanine‑restricted diet during treatment. Ensure recent Phe level (within 90 days) and diet adherence evidence are included.

Pediatric age documentation (member ≥ 12 years) when applicable
Recent Phe blood level within 90 days (>600 µmol/L for initiation)
Evidence of current and ongoing adherence to a phenylalanine‑restricted diet

Note

Medicaid Precedence

For Medicaid members, state Medicaid coverage provisions take precedence. If state provisions conflict with this policy, the state Medicaid manual should be consulted and may lead to denial if coverage differs.

State Medicaid rules supersede this clinical policy when in conflict

AbbreviationPhe = phenylalanine

inv-24: Adherence to a phenylalanine‑restricted diet as part of PKU management

DefinitionAdherence to a phenylalanine‑restricted diet means the member is currently following and will continue a Phe‑restricted diet as part of PKU management.

Coverage requirementDocumentation of diet adherence is required for initial and continued approval per updated criteria.

Policy rationaleDiet adherence was added to align with plan feedback and Sephience criteria and is required alongside pharmacologic therapy.