PALYNZIQ, Pegvaliase-pqpz Form

Pegvaliase-pqpz (Palynziq™) is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with phenylketonuria (PKU) and reduces blood phenylalanine concentrations. FDA Approved Indication(s) Palynziq is indicated to reduce blood phenylalanine concentrations in adult patients with PKU who have uncontrolled blood phenylalanine concentrations > 600 µmol/L on existing management. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Palynziq is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Phenylketonuria (must meet all):

1. Diagnosis of PKU;
   2. Prescribed by or in consultation with an endocrinologist, metabolic disease specialist, or genetic disease specialist;
2. Age ≥ 18 years;
   
   4. Recent (within 90 days) phenylalanine (Phe) blood level is > 600 µmols/L;
   5. Member is currently on a phenylalanine-restricted diet and will continue this diet during treatment with Palynziq;

3. Failure of Kuvan® at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;

   7. Palynziq is not prescribed concurrently with Kuvan;
   8. Dose does not exceed 20 mg per day. Approval duration:
      Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer Page 1 of 7

   CLINICAL POLICY Pegvaliase-pqpz B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Phenylketonuria (must meet all):
6. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
7. Member is currently on a phenylalanine-restricted diet and will continue this diet during treatment with Palynziq;
8. Member meets one of the following (a, b, or c): a. Member has achieved blood Phe control (i.e., blood Phe level is ≤ 600 µmol/L); b. Request is for 40 mg per day and member has previously used 20 mg per day continuously for at least 6 months without achieving blood Phe control; c. Request is for 60 mg per day and member meets both of the following (i and ii):
   i. Member has previously used 40 mg per day continuously for at least 16 weeks without achieving blood Phe control; ii. Member has not used 60 mg per day continuously for more than 16 weeks without achieving blood Phe control;
9. If request is for a dose increase, new dose does not exceed 60 mg per day. Approval duration:
   Medicaid/HIM – 12 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

10. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): Page 2 of 7

    CLINICAL POLICY Pegvaliase-pqpz a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

11. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration PAH: phenylalanine hydroxylase PAL: phenylalanine ammonia lyase Phe: phenylalanine PKU: phenylketonuria Dose Limit/ Maximum Dose 20 mg/kg/day
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Kuvan (sapropterin) Age 1 month to ≤ 6 years (starting dose): 10 mg/kg PO QD
    Age ≥ 7 years (starting dose): 10 to 20 mg/kg PO QD
    Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): risk of anaphylaxis Appendix D: General Information
    • Palynziq has a black box warning for the potential to cause anaphylaxis and enrollment in a REMS program is required, along with supervision of the initial dose by a healthcare professional and the need to carry auto-injectable epinephrine at all times while using Page 3 of 7

    CLINICAL POLICY Pegvaliase-pqpz Palynziq. Use of premedication with H1 blockers, H2 blockers, and/or antipyretics can also be considered. • Per the Palynziq PI, discontinuation of Palynziq is recommended if a patient has not achieved an adequate response (blood Phe concentration ≤ 600 µmol/L) after 16 weeks of continuous treatment with the maximum dosage of 60 mg QD. V. Dosage and Administration
    Indication Dosing Regimen PKU Initiate dosing with 2.5 mg SC once weekly for 4 weeks. Administer the initial dose under the supervision of a healthcare provider. Maximum Dose 60 mg/day Titrate the Palynziq dosage in a step-wise manner, based on tolerability, over ≥ 5 weeks, to achieve a dosage of 20 mg SC QD. Maintain the Palynziq dosage at 20 mg SC QD for ≥ 24 weeks. Consider increasing the Palynziq dosage to 40 mg SC QD in patients who have been maintained continuously on 20 mg QD for ≥ 24 weeks and who have not achieved a blood Phe concentration ≤ 600 µmol/L. Consider increasing the dosage to a maximum of 60 mg SC QD in patients who have been on 40 mg QD continuously for ≥ 16 weeks and who have not achieved a blood Phe concentration ≤ 600 µmol/L. Discontinue Palynziq in patients who have not achieved a response (blood Phe concentration ≤ 600 µmol/L) after 16 weeks of continuous treatment with the maximum dosage of 60 mg QD. VI. Product Availability
    Injection, single-dose prefilled syringe: 2.5 mg/0.5 mL, 10 mg/0.5 mL, 20 mg/mL VII.