Asfotase Alfa (Strensiq) Form

Asfotase alfa (Strensiq®) is a tissue nonspecific alkaline phosphatase. FDA Approved Indication(s) Strensiq is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP). 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 Strensiq is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Perinatal/Infantile- and Juvenile-Onset Hypophosphatasia (must meet all):

1. Diagnosis of perinatal/infantile- or juvenile-onset HPP as evidenced by all of the following (a, b, and c):
   a. Age of onset is < 18 years;
   b. Presence of one of the following laboratory indices (i or ii):
   i. Mutation in the ALPL gene encoding for tissue non-specific alkaline phosphatase (TNSALP)*; ii. Serum alkaline phosphatase (ALP) below the age-adjusted normal range and either of the following (a or b): a) Plasma pyridoxal 5’-phosphate (PLP; main circulating form of vitamin B6) above the upper limit of normal (ULN); b) Urinary phosphoethanolamine (PEA) above the ULN; c. History of one of the following HPP clinical manifestations (i, ii, iii, or iv):
   i. Vitamin B6-dependent seizures; ii. Failure to thrive or growth failure/short stature; iii. Nephrocalcinosis with hypercalcemia/hypercalciuria; iv. Skeletal abnormalities and associated impairments (any of the following): a) Craniosynostosis (premature fusion of one or more cranial sutures) with increased intracranial pressure;
   b) Rachitic chest deformity (costochondral junction enlargement seen in advanced rickets) with associated respiratory compromise; c) Limb deformity with delayed walking or gait abnormality; Page 1 of 6

   CLINICAL POLICY
   Asfotase Alfa d) Compromised exercise capacity due to rickets and muscle weakness; e) Low bone mineral density for age with unexplained fractures; f) Alveolar bone loss with premature loss of deciduous (primary) teeth;

2. Prescribed by or in consultation with an endocrinologist;
   3. Dose does not exceed the following (a or b): a. Perinatal/infantile-onset HPP: 9 mg/kg per week; b. Juvenile-onset HPP: 6 mg/kg per week. Approval duration:
      Medicaid/HIM – 6 months Commercial – 6 months or to member’s renewal date, whichever is longer _ *TNSALP is an ALP isoenzyme; a functional mutation in the gene (ALPL) encoding for TNSALP results in low TNSALP activity (as evidenced by a low serum ALP level) and increased levels of TNSALP substrates (PLP and PEA). B. Other diagnoses/indications (must meet 1 or 2):
3. 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
4. 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. Perinatal/Infantile- and Juvenile-Onset Hypophosphatasia (must meet all):
5. 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);

6. Member is responding positively to therapy, as evidenced by improvement in any of the following on initial re-authorization request:
   a. Height velocity; b. Respiratory function; Page 2 of 6

   CLINICAL POLICY
   Asfotase Alfa c. Skeletal manifestations (e.g., bone mineralization, bone formation and remodeling, fractures, deformities); d. Motor function, mobility, or gait;

7. If request is for a dose increase, new dose does not exceed the following (a or b): a. Perinatal/infantile-onset HPP: 9 mg/kg per week; b. Juvenile-onset HPP: 6 mg/kg per week. Approval duration:
   Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer 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 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

9. 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 ALP: alkaline phosphatase FDA: Food and Drug Administration HPP: hypophosphatasia PEA: phosphoethanolamine Appendix B: Therapeutic Alternatives Not applicable PLP: pyridoxal 5’-phosphate TNSALP: tissue non-specific alkaline phosphatase ULN: upper limit of normal Page 3 of 6

   CLINICAL POLICY
   Asfotase Alfa Appendix C: Contraindications/Boxed Warnings None reported V. Dosage and Administration
   Indication Perinatal/infantile- onset HPP
   Dosing Regimen 6 mg/kg SC per week as either: • 2 mg/kg three times per week, or • 1 mg/kg six times per week Maximum Dose 9 mg/kg/week The dose may be increased for lack of efficacy (e.g., no improvement in respiratory status, growth, or radiographic findings) up to 9 mg/kg per week, administered as 3 mg/kg SC three times per week. Juvenile-onset HPP 6 mg/kg SC per week as either: 6 mg/kg/week • 2 mg/kg three times per week, or • 1 mg/kg six times per week VI. Product Availability
   Single-use vials: 18 mg/0.45 mL, 28 mg/0.7 mL, 40 mg/mL, 80 mg/0.8 mL VII.