Sodium Phenylbutyrate (Buphenyl) Form

Sodium phenylbutyrate (Buphenyl®, Pheburane®, Olpruva™) is a nitrogen-binding agent. FDA Approved Indication(s) Buphenyl is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS).
Pheburane is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients with UCDs, involving deficiencies of CPS, OTC or AS. Olpruva is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients weighing 20 kg or greater and with a body surface area (BSA) of 1.2 m2 or greater, with UCDs involving deficiencies of CPS, OTC, or AS.
Limitation(s) of use: Buphenyl, Pheburane, and Olpruva should not be used to manage acute hyperammonemia, which is a medical emergency. 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 Buphenyl, Pheburane, and Olpruva are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Urea Cycle Disorder: CPS, OTC, AS (must meet all):

1. Diagnosis of a UCD caused by one or more of the following, confirmed by enzymatic, biochemical, or genetic analysis: a. CPS deficiency; b. OTC deficiency; c. AS deficiency;

2. Prescribed by or in consultation with a physician experienced in treating metabolic disorders;
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   CLINICAL POLICY
   Sodium Phenylbutyrate

3. If request is for Olpruva and age < 18 years, member meets both of the following (a and b): a. Weight ≥ 20 kg; b. BSA ≥ 1.2 m2;
4. Member must use generic sodium phenylbutyrate tablets or powder, unless contraindicated or clinically significant adverse events are experienced;
5. Dose does not exceed 20 grams per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
6. 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
7. 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 Approval
   A. Urea Cycle Disorder: CPS, OTC, AS (must meet all):
8. 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);
9. If request is for Olpruva and age < 18 years, member meets both of the following (a and b): a. Weight ≥ 20 kg; b. BSA ≥ 1.2 m2;
10. Member must use generic sodium phenylbutyrate tablets or powder, unless contraindicated or clinically significant adverse events are experienced;

11. Member is responding positively to therapy;

    5. If request is for a dose increase, new dose does not exceed 20 grams per day. Approval duration: 12 months Page 2 of 6

    CLINICAL POLICY
    Sodium Phenylbutyrate B. Other diagnoses/indications (must meet 1 or 2):

12. 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

13. 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 policy – 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 ASL: argininosuccinate lyase AS: argininosuccinate synthetase BSA: body surface area CPSI: carbamyl phosphate synthetase 1
    CTLN1: type I citrullinemia Appendix B: Therapeutic Alternatives
    Not applicable
    FDA: Food and Drug Administration NAGS: N-acetyl glutamate synthetase OTC: ornithine transcarbamylase UCD: urea cycle disorder Appendix C: Contraindications/Boxed Warnings • Contraindication(s): should not be used to manage acute hyperammonemia (Buphenyl only) • Boxed warning(s): none reported Appendix D: Urea Cycle Disorders UCDs are caused by a deficiency in any of the below enzymes in the pathway that transforms nitrogen to urea: • Carbamyl phosphate synthetase 1 (CPS1) deficiency • Ornithine transcarbamylase (OTC) deficiency Page 3 of 6

    CLINICAL POLICY
    Sodium Phenylbutyrate • Argininosuccinate synthetase (AS) deficiency (also known as classic citrullinemia or type I citrullinemia, CTLN1) • Argininosuccinate lyase (ASL) deficiency (also known as argininosuccinic aciduria) • N-acetyl glutamate synthetase (NAGS) deficiency • Arginase deficiency V. Dosage and Administration
    Drug Name Sodium phenylbutyrate (Buphenyl, Pheburane) Sodium phenylbutyrate (Olpruva) Dosing Regimen Weight < 20 kg: 450-600 mg/kg/day PO in three to six equally divided doses with each meal or feeding Weight ≥ 20 kg: 9.9-13 g/m2/day PO in three to six equally divided doses with each meal or feeding 9.9-13 g/m2/day PO in three to six equally divided doses with food Maximum Dose 20 grams/day 20 grams/day VI. Product Availability
    Drug Name Sodium phenylbutyrate (Buphenyl) Availability • Tablet: 500 mg • Powder: 250 grams (each level tablespoon dispenses 8.6 Sodium phenylbutyrate (Pheburane) Sodium phenylbutyrate (Olpruva) grams of Buphenyl) Oral pellets: 84 g of sodium phenylbutyrate per bottle Oral suspension pellets in packets for reconstitution: 2 g, 3 g, 4 g, 5 g, 6 g, and 6.67 g
    VII.