ZAVESCA, Miglustat Form

Miglustat (Zavesca®) is a glucosylceramide synthase inhibitor. FDA Approved Indication(s) Zavesca is indicated as monotherapy for the treatment of adult patients with mild/moderate type 1 Gaucher disease (GD1) for whom enzyme replacement therapy is not a therapeutic option. 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 Zavesca is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Type 1 Gaucher Disease (must meet all):

1. Diagnosis of GD1 confirmed by one of the following (a or b): a. Enzyme assay demonstrating a deficiency in beta-glucocerebrosidase (glucosidase) activity; b. DNA testing;
2. Age ≥ 18 years;
   3. Member is symptomatic (e.g., anemia, thrombocytopenia, bone disease, hepatomegaly, splenomegaly);
3. Failure of two enzyme replacement therapies (i.e., Cerezyme®, Elelyso®, VPRIV®), unless member is unable to take enzyme replacement therapies due to one of the following (a or b): a. Allergy or hypersensitivity;
   b. Poor venous access;

4. Zavesca is prescribed as monotherapy;

   6. Dose does not exceed both of the following (a and b): a. 300 mg per day; b. 3 capsules per day. Approval duration: 6 months Page 1 of 6

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   Miglustat B. Other diagnoses/indications (must meet 1 or 2):

5. 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
6. 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. Type 1 Gaucher Disease (must meet all):
7. 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 increased or stabilized platelet count or hemoglobin, reduced or stabilized spleen or liver volume, or decreased bone pain;
9. Zavesca is prescribed as monotherapy;
   
   4. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 300 mg per day; b. 3 capsules per day. Approval duration: 12 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 Page 2 of 6

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    Miglustat 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 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 FDA: Food and Drug Administration GD1: type 1 Gaucher disease
    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.
    Dosing Regimen Drug Name Cerezyme
    (imiglucerase)
    Individualize to each patient; initial dose ranges from 2.5 units/kg by IV infusion 3 times a week to 60 units/kg once every 2 weeks; disease severity may dictate treatment be initiated at relatively high dose or relatively frequent administration 60 units/kg IV every other week Elelyso (taliglucerase alfa) VPRIV (velaglucerase alfa) 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. 60 units/kg IV every other week Individualized
    Individualized
    Dose Limit/ Maximum Dose Individualized
    Appendix C: Contraindications/Boxed Warnings None reported Page 3 of 6

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    Miglustat Appendix D: General Information • GD1 is a heterogeneous disorder which involves the visceral organs, bone marrow, and bone in almost all affected patients. Common conditions resulting from GD1 include anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone disease. Therefore, hemoglobin level, platelet count, liver volume, spleen volume, and bone pain are clinical parameters that can indicate therapeutic response to GD1 therapies. In some clinical trials, stability has been defined as the following thresholds of change from baseline: hemoglobin level < 1.5 g/dL decrease, platelet count < 25% decrease, liver volume < 20% increase, and spleen volume < 25% increase. • There is currently insufficient evidence that supports the combination use of enzyme replacement therapy with Zavesca.
    V. Dosage and Administration
    Indication GD1 Dosing Regimen 100 mg PO TID VI. Product Availability
    Capsule: 100 mg Maximum Dose 300 mg/day VII.