CERDELGA, Eliglustat Tartrate Form

Eliglustat (Cerdelga®) is a glucosylceramide synthase inhibitor. FDA Approved Indication(s) Cerdelga is indicated for the long-term treatment of adult patients with type 1 Gaucher disease (GD1) who are CYP2D6 extensive metabolizers, intermediate metabolizers, or poor metabolizers as detected by an FDA-cleared test. Limitation(s) of use:
• CYP2D6 ultra-rapid metabolizers may not achieve adequate concentrations of Cerdelga to achieve a therapeutic effect. • A specific dosage cannot be recommended for CYP2D6 indeterminate metabolizers. 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 Cerdelga 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 of beta-glucocerebrosidase (glucosidase) activity; b. DNA testing;
2. Age ≥ 18 years;
   3. Member is symptomatic (e.g., anemia, thrombocytopenia, bone disease, hepatomegaly, splenomegaly);
3. Member is positive for one of the following CYP2D6 genotypes as detected by an FDA-cleared test (a, b, or c): a. Extensive metabolizer (EM); b. Intermediate metabolizer (IM); c. Poor metabolizer (PM);

4. Cerdelga is prescribed as monotherapy; Page 1 of 6

   CLINICAL POLICY Eliglustat

5. Dose does not exceed: a. CYP2D6 EMs and IMs (both i and ii):
   i. 168 mg per day; ii. 2 capsules per day; b. CYP2D6 PMs (both i and ii):
   i. 84 mg per day; ii. 1 capsule 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 Therapy A. Type 1 Gaucher Disease (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. Member is responding positively to therapy as evidenced by increased or stabilized platelet count or hemoglobin level, reduced or stabilized spleen or liver volume, or decreased bone pain;

10. Cerdelga is prescribed as monotherapy;

    4. If request is for a dose increase, new dose does not exceed: a. CYP2D6 EMs and IMs (both i and ii):
       i. 168 mg per day; ii. 2 capsules per day; b. CYP2D6 PMs (both i and ii):
       i. 84 mg per day; ii. 1 capsule per day. Page 2 of 6

    CLINICAL POLICY Eliglustat Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

11. 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

12. 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 policies – 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 EM: extensive metabolizer FDA: Food and Drug Administration GD1: type 1 Gaucher disease Appendix B: Therapeutic Alternatives
    Not applicable
    IM: intermediate metabolizer PM: poor metabolizer Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o For EMs – taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor; moderate or severe hepatic impairment; mild hepatic impairment taking a strong or moderate CYP2D6 inhibitor o For IMs – taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor; taking a strong CYP3A inhibitor; any degree of hepatic impairment o For PMs – taking a strong CYP3A inhibitor; any degree of hepatic impairment • Boxed warning(s): none reported Page 3 of 6

    CLINICAL POLICY Eliglustat 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 Cerdelga. • A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers). V. Dosage and Administration
    Indication GD1 Dosing Regimen CYP2D6 EM, IM: 84 mg PO BID CYP2D6 PM: 84 mg PO QD Maximum Dose CYP2D6 EM, IM: 168 mg/day CYP2D6 PM: 84 mg/day VI. Product Availability
    Capsule: 84 mg VII.