KUVAN, Sapropterin Dihydrochloride Form

Sapropterin dihydrochloride (Kuvan®) is a synthetic form of tetrahydrobiopterin (BH4), the cofactor for the enzyme phenylalanine hydroxylase. FDA Approved Indication(s) Kuvan is indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive phenylketonuria (PKU). Kuvan is to be used in conjunction with a Phe-restricted diet. Policy/Criteria Provider must submit documentation (including 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 Kuvan is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Phenylketonuria (must meet all):

1. Diagnosis of HPA due to PKU;
2. Prescribed by or in consultation with a metabolic or genetic disease specialist;
3. Recent (within 90 days) Phe blood level is > 360 µmols/L;
4. Member is currently on a Phe-restricted diet and will continue this diet during treatment with Kuvan;
   5. Kuvan is not prescribed concurrently with Palynziq®;

5. If request is for brand Kuvan, member must use generic sapropterin, unless contraindicated or clinically significant adverse effects are experienced;

   7. Dose does not exceed 20 mg/kg per day. Approval duration: 3 months B. Other diagnoses/indications (must meet 1 or 2):
   8. 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 Page 1 of 5

   CLINICAL POLICY Sapropterin Dihydrochloride 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

   2. 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):
   3. 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);
   4. Member is responding positively to therapy as demonstrated by a reduction in Phe blood levels since initiation of therapy;
   5. Member is currently on a Phe-restricted diet and will continue this diet during treatment with Kuvan;
   6. If request is for brand Kuvan, member must use generic sapropterin, unless contraindicated or clinically significant adverse effects are experienced;

6. If request is for a dose increase, new dose does not exceed 20 mg/kg per day. Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

   1. 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
   2. 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.
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   CLINICAL POLICY Sapropterin Dihydrochloride 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, CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key BH4: tetrahydrobiopterin HPA: hyperphenylalaninemia Appendix B: Therapeutic Alternatives Not applicable Appendix C: Contraindications/Boxed Warnings None reported Phe: phenylalanine PKU: phenylketonuria Appendix D: General Information • According to the Prescribing Information, if a 10 mg/kg per day starting dose is used, then response to therapy is determined by change in blood Phe following treatment with Kuvan at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Kuvan treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg per day, the dose may be increased to 20 mg/kg per day. Additionally, regardless of starting dose, patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg per day are non-responders and treatment with Kuvan should be discontinued in these patients. V. Dosage and Administration
   Indication Dosing Regimen BH4- responsive PKU 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 Maximum Dose 20 mg/kg/day VI. Product Availability
   • Tablet: 100 mg • Powder for oral solution: 100 mg, 500 mg VII.