SIGNIFOR, Pasireotide Diaspartate SIGNIFOR LAR, Pasireotide Pamoate Form

Pasireotide (Signifor®, Signifor® LAR) is a somatostatin analog. ____ *For Health Insurance Marketplace (HIM), if request is through pharmacy benefit, Signifor LAR is non-formulary and cannot be approved using these criteria; refer to the formulary exception policy, HIM.PA.103. FDA Approved Indication(s) Signifor and Signifor LAR are indicated for the treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. Signifor is specifically indicated in adults. Signifor LAR is also indicated for the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an 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 Signifor and Signifor LAR are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acromegaly (must meet all):

1. Diagnosis of acromegaly as evidenced by one of the following (a or b): a. Pre-treatment insulin-like growth factor-I (IGF-I) level above the upper limit of normal based on age and gender for the reporting laboratory; b. Serum growth hormone (GH) level ≥ 1 µg/mL after a 2-hour oral glucose tolerance test;
2. Request is for Signifor LAR;
   3. Prescribed by or in consultation with an endocrinologist;
   4. Age ≥ 18 years;
   5. Inadequate response to surgical resection or pituitary irradiation (see Appendix D), or member is not a candidate for such treatment;

3. Dose does not exceed (a and b): a. 60 mg every 4 weeks; b. 1 vial every 4 weeks. Approval duration:
   Medicaid – 6 months
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   CLINICAL POLICY Pasireotide HIM – refer to HIM.PA.103 for Signifor LAR Commercial – 6 months or to the member’s renewal date, whichever is longer B. Cushing’s Disease (must meet all):

   1. Diagnosis of Cushing’s disease;
   2. Prescribed by or in consultation with an endocrinologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a or b): a. Pituitary surgery was not curative; b. Member is not eligible for pituitary surgery;
   5. Dose does not exceed one of the following (a or b): a. Signifor (i and ii):
      i. 1.8 mg per day; ii. 2 ampules per day; b. Signifor LAR (i and ii):
      i. 40 mg every 4 weeks ii. 1 vial every 4 weeks. Approval duration:
      Medicaid – 6 months
      HIM – 6 months for Signifor (refer to HIM.PA.103 for Signifor LAR) Commercial – 6 months or to the member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2):
4. 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
5. 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. Acromegaly (must meet all):

6. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 7

   CLINICAL POLICY Pasireotide 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);

7. Request is for Signifor LAR;
   3. Member is responding positively to therapy (see Appendix D);
   4. If request is for a dose increase, new dose does not exceed (a and b): a. 60 mg every 4 weeks; b. 1 vial every 4 weeks. Approval duration:
      Medicaid – 12 months
      HIM – refer to HIM.PA.103 for Signifor LAR
      Commercial – 12 months or to the member’s renewal date, whichever is longer B. Cushing’s 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 (see Appendix D);
   3. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. Signifor (i and ii):
      i. 1.8 mg per day; ii. 2 ampules per day; b. Signifor LAR (i and ii):
      i. 40 mg every 4 weeks; ii. 1 vial every 4 weeks. Approval duration:
      Medicaid – 12 months
      HIM – 12 months for Signifor (refer to HIM.PA.103 for Signifor LAR) Commercial – 6 months or to the member’s renewal date, whichever is longer C. 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: Page 3 of 7

    CLINICAL POLICY Pasireotide 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 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 FDA: Food and Drug Administration GH: growth hormone IGF-I: insulin-like growth factor Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings None reported
    Appendix D: General Information • Treatment response for Cushing’s disease may be defined as reduction in 24-hour urinary free cortisol (UFC) levels and/or improvement in signs or symptoms of the disease. Maximum urinary free cortisol reduction is typically seen by two months of treatment. • Examples of treatment response to acromegaly therapy (including somatostatin analogs, surgical resection or pituitary irradiation) include improvement from baseline in or normalization of GH and/or age- and sex-adjusted IGF-I serum concentrations, or tumor mass control. V. Dosage and Administration
    Indication Cushing’s disease Drug Name Pasireotide (Signifor) Dosing Regimen Initial: 0.6 mg or 0.9 mg SC BID Maximum Dose 1.8 mg/day Recommended dosing range: 0.3 mg to 0.9 mg SC BID 10 mg to 40 mg IM every 4 weeks Pasireotide (Signifor LAR) Cushing’s disease Acromegaly Signifor LAR must be administered by a healthcare professional 40 mg to 60 mg IM every 4 weeks 40 mg/4 weeks 60 mg/4 weeks Page 4 of 7

    CLINICAL POLICY Pasireotide VI. Product Availability
    Drug Name Pasireotide (Signifor) Pasireotide (Signifor LAR) Availability Single-dose ampules for injection: 0.3 mg/mL, 0.6 mg/mL, 0.9 mg/mL
    Vials for reconstitution and injectable suspension: 10 mg, 20 mg, 30 mg, 40 mg, 60 mg VII.