Olipudase alfa (GZ402665) Form

Olipudase alfa-rpcp (Xenpozyme™) is a hydrolytic lysosomal sphingomyelin-specific enzyme. FDA Approved Indication(s) Xenpozyme is indicated for treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
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 Xenpozyme is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acid Sphingomyelinase Deficiency (must meet all):

1. Diagnosis of ASMD confirmed by one of the following (a or b): a. Enzyme assay demonstrating a deficiency of acid sphingomyelinase activity; b. DNA testing;
2. A diagnosis of Gaucher disease has been ruled out by determination of glucocerebrosidase activity;
3. Member has ASMD Type B or Type A/B;
   4. For members aged ≥ 18 years, member has all of the following (a, b, and c): a. Diffuse capacity of the lung for carbon monoxide (DLco) ≤ 70%; b. Spleen volume ≥ 6 multiples of normal (MN) as measured by magnetic resonance imaging (MRI); c. Splenomegaly related score (SRS) ≥ 5;
4. For members aged < 18 years, member has both of the following (a and b): a. Spleen volume ≥ 5 MN as measured by MRI; b. Height Z-score ≤ -1;

5. Documentation of member’s weight (in kg);

   7. Dose does not exceed 3 mg/kg every two weeks. Approval duration: 6 months
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   CLINICAL POLICY Olipudase Alfa-rpcp 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 Therapy A. Acid Sphingomyelinase Deficiency (must meet all):
   
   1. 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);
8. Member is responding positively to therapy as evidenced by improvement in, but not limited to, any of the following parameters: lung function, reduced or stabilized spleen volume, or (in pediatrics only) improved height Z-scores (see Appendix D for examples of individual patients’ ASMD disease manifestation profiles);
9. Documentation of member’s weight (in kg);
   4. If request is for a dose increase, new dose does not exceed 3 mg/kg every two weeks. Approval duration: 6 months
      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): 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 Page 2 of 6

    CLINICAL POLICY Olipudase Alfa-rpcp

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 2 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; B. ASMD Type A. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ASMD: acid sphingomyelinase deficiency DLco: diffuse capacity of the lung for carbon monoxide Appendix B: Therapeutic Alternatives
    Not applicable FDA: Food and Drug Administration MN: multiples of normal MRI: magnetic resonance imaging SRS: splenomegaly related score Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): hypersensitivity reactions including anaphylaxis
    Appendix D: General Information
    • Individual patient manifestations of ASMD may include hepatomegaly, splenomegaly, bleeding/bruising, thrombocytopenia, dyslipidemia, interstitial lung disease (with decreased DLco), delayed growth and puberty, osteoporosis/osteopenia, liver dysfunction with progressive fibrosis, and cardiac disease. • ASMD Type A (infantile neurovisceral disease) includes severe neurologic symptoms and is uniformly fatal in early childhood. Olipudase alfa does not cross the blood-brain barrier and thus is not appropriate for the treatment of patients with ASMD Type A. • ASMD and Gaucher disease have several clinical manifestations in common. Simultaneous determination of acid sphingomyelinase activity and glucocerebrosidase activity to distinguish ASMD from Gaucher disease is recommended. V. Dosage and Administration Indication ASMD Type B and Type A/B Dosing Regimen Pediatrics: IV dosing every 2 weeks starting with 0.03 mg/kg/dose titrated to a final target maintenance dose by Week 16 of 3 mg/kg every 2 weeks Maximum Dose 3 mg/kg every 2 weeks Page 3 of 6

    CLINICAL POLICY Olipudase Alfa-rpcp Indication Dosing Regimen Adults: IV dosing every 2 weeks starting with 0.1 mg/kg/dose titrated to a final target maintenance dose by Week 14 of 3 mg/kg every 2 weeks Maximum Dose VI. Product Availability
    Vial with lyophilized powder for reconstitution: 20 mg VII.