PARSABIV, Etelcalcetide HCl Form

Etelcalcetide (Parsabiv®) is a calcium-sensing receptor agonist which binds to the calcium- sensing receptor (CaSR) on chief cells of the parathyroid gland. FDA Approved Indication(s) Parsabiv is indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.
Limitation(s) of use: Parsabiv has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with CKD who are not on hemodialysis and is not recommended for use in these populations. 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 Parsabiv is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Secondary Hyperparathyroidism (must meet all):

1. Diagnosis of secondary HPT associated with CKD;
   2. Prescribed by or in consultation with a nephrologist or endocrinologist;
   3. Age ≥ 18 years;
   4. Member is on hemodialysis;
   5. Lab results over the previous 3-6 months show trending increase in iPTH level or current (within the last 30 days) labs show iPTH above the normal levels;
2. Failure of Sensipar® and a vitamin D analog (see Appendix B) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;
   *Prior authorization may be required for Sensipar
   7. Member is not receiving other calcimimetics;
   8. At the time of request, member does not have serum calcium less than the lower limit of the normal range;

3. Dose does not exceed 15 mg three times per week. Approval duration: 6 months Page 1 of 7

   CLINICAL POLICY Etelcalcetide B. 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Secondary Hyperparathyroidism (must meet all):
   3. 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);
5. Member is responding positively to therapy as evidenced by a decrease in iPTH;
   3. Member is not receiving other calcimimetics;
   4. If request is for a dose increase, new dose does not exceed 15 mg three times per week.
      Approval duration: 12 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: 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: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

   2. 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: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid.
      Page 2 of 7

   CLINICAL POLICY Etelcalcetide 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 – 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 CaSR: calcium-sensing receptor
   CKD: chronic kidney disease
   HPT: hyperparathyroidism iPTH: intact parathyroid hormone PTH: parathyroid hormone 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.
   Drug Name Dosing Regimen cinacalcet (Sensipar®) calcitriol
   (Rocaltrol®) doxercalciferol (Hectorol®) paricalcitol (Zemplar®) 30 mg PO QD; titrate as necessary no more frequently than every 2 to 4 weeks through sequential doses of 60 mg, 90 mg, 120 mg, and 180 mg PO QD
   Oral: 0.25 mcg PO QD or QOD; may increase dose by 0.25 mcg/day at 4 to 8 week intervals IV: 1 to 2 mcg/day IV 3 times weekly on approximately every other day; may increase by 0.5 to 1 mcg/dose at 2 to 4 week intervals
   Oral: 10 mcg PO 3 times weekly at dialysis; increase dose as needed at 8 week intervals in 2.5 mcg increments if iPTH is not lowered by 50% and fails to reach the target range
   IV: 4 mcg IV bolus 3 times weekly at the end of dialysis, increase dose as needed at 8 week intervals by 1 to 2 mcg increments if iPTH is not lowered by 50% and fails to reach the target range
   1 mcg PO daily if baseline iPTH level is 500 picog/mL or less; 2 mcg PO daily if baseline iPTH level is greater than 500 picog/mL; may titrate dose at 2 to 4 week intervals Dose Limit/ Maximum Dose 300 mg/day Oral: 1 mcg/day IV: 4 mcg/day Oral: 20 mcg 3 times weekly IV: 18 mcg/week 0.24 mcg/kg 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): known hypersensitivity to etelcalcetide or any of its excipients • Boxed warning(s): none reported Page 3 of 7

   CLINICAL POLICY Etelcalcetide Appendix D: General Information • • Secondary hyperparathyroidism (HPT) is most commonly seen in patients with chronic kidney disease (CKD). These patients present with elevated levels of parathyroid hormone (PTH) and an enlarged parathyroid gland. Increased levels of PTH result from vitamin D deficiency, hypocalcemia and hyperphosphatemia; all attributed to kidney failure. Over time, as kidney function deteriorates, secondary HPT becomes more severe and may lead to abnormalities in bone mineralization and turnover and soft tissue and vascular calcifications.
   Parsabiv treats secondary HPT in patients with CKD who are on dialysis. The maintenance dose of Parsabiv is individualized and titrated based on PTH and corrected serum calcium response. The dose may be increased by 2.5-5 mg no more frequently than every 4 weeks. Serum calcium levels should be measured 1 week after initiation of therapy or dosage adjustment, and every 4 weeks thereafter for maintenance. Also, PTH should be measured 4 weeks after initiation of therapy or dose adjustment. In individuals with PTH levels below the target range, reduce the dose of Parsabiv or temporarily stop the therapy. Once PTH and serum calcium levels return to the target range, therapy will be initiated at a lower dose. Among individuals with a corrected serum calcium of at least 7.5 mg/dL but below target range and without symptoms of hypocalcemia, consider reducing the dose, temporarily stopping therapy, or adding on therapies to increase serum calcium. If therapy is stopped, reinitiate at a lower dose when PTH and serum calcium levels return to the target range. If the corrected serum calcium falls below 7.5 mg/dL, or if patient is experiencing symptomatic hypocalcaemia, stop the therapy and treat hypocalcaemia. • Cinacalcet should be discontinued for at least 7 days prior to starting Parsabiv. • If serum calcium falls below 7.5 mg/dL or if patient reports symptoms of hypocalcemia, therapy should be discontinued. V. Dosage and Administration
   Indication Secondary HPT Initial: 5 mg IV bolus 3 times per week Dosing Regimen administered at the end of hemodialysis; adjust in 2.5 or 5 mg increments no more frequently than every 4 weeks to maintain target PTH levels and normal serum calcium levels. Maximum Dose 15 mg three times per week
   VI. Product Availability
   Solution in a single-dose vial for injection: 2.5 mg/0.5 mL, 5 mg/mL, 10 mg/2 mL
   VII.