The FDA approval of Parsabiv was based on two 26-week, randomized, double-blind, placebo controlled studies. An aggregate of 1,023 patients with moderate-to-severe secondary HPT (PTH greater than 400 pg/mL) on hemodialysis were randomized to receive intravenous Parsabiv or placebo three times a week, at the end of their dialysis sessions in addition to standard of care that could include vitamin D and/or phosphate binders. The primary endpoint of both studies was the proportion of patients achieving greater than 30 percent reduction from baseline in PTH during the Efficacy Assessment Phase (EAP), defined as weeks 20 through 27. Secondary endpoints included the proportion of patients with PTH less than or equal to 300 pg/mL during the EAP; and percent reductions in PTH, albumin-adjusted calcium (cCa), phosphate (P) and cCa x P during the EAP. The two studies showed that significantly more Parsabiv than placebo patients, respectively, achieved; a greater than 30 percent reduction from baseline in PTH during the EAP: 77% versus 11% in Study 1, and 79% versus 11% in Study 2. PTH levels of 300 pg/mL or less during the EAP: 52% versus 6% in Study 1, and 56% versus 5% in Study. Additionally, greater percent reduction from baseline was achieved in Parsabiv-treated patients than placebo treated patients during the EAP, for PTH, corrected calcium and phosphate in both studies

The most common side effects that occurred were muscle spasms, diarrhea, nausea and hypocalcemia.

Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)

I. Parsabiv (Etelcalcetide) is medically necessary for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on hemodialysis when all of the following criteria are met:
a. Member must be 18 years of age or older AND

b. Member must have moderate to severe hyperparathyroidism (PTH ≥400 pg/ml) AND

c. Member must be receiving hemodialysis 3 times weekly for at least 3 months AND

d. Member must not have any contraindication such as known hypersensitivity to Parsabiv AND

e. Member’s corrected calcium level is at or above the lower limit of normal prior to initiation (≥8.3 mg/dL) AND

f. Member must be taking stable doses of active vitamin D analogs or calcium supplements or phosphate binders AND

g. Member must have previous trial and failure, contraindication, or side effect/intolerance with a cinacalcet containing product (Sensipar) AND

h. If member is switching from Cinacalcet (Sensipar) to Parsabiv, member must discontinue Cinacalcet at least 7 days prior to starting Parsabiv and member must not be using Parsabiv concurrently with Cinacalcet. AND

i. The prescriber is a specialist in the area of the patient's diagnosis (e.g. endocrinologist, nephrologist) or has consulted with a specialist in the area of the patient's diagnosis



[INFORMATIONAL NOTE: As per the FDA labeled package insert indication and usage section, Parsabiv (etelcalcetide) has not been studied in adult patients with parathyroid carcinoma, primary hyperparathyroidism, or with chronic kidney disease who are not on hemodialysis and is not recommended for use in these populations.

According to the package insert, steady-state drug levels of Sensipar are achieved within 7 days.

A head-to-head study between Sensipar and Parsabiv compared the efficacy and safety of IV Parsabiv and oral Sensipar in 683 patients with sHPT on hemodialysis. Patients receiving maintenance hemodialysis three times per week with sHPT (pre-dialysis serum PTH>500 pg/mL) on stable doses of calcium supplements or phosphate binders and calcitriol or active vitamin D analogs, if prescribed, with albumin-corrected serum calcium >8.3 mg/dL were eligible for participation. The use of Sensipar during 3 months prior was an exclusion criteria. The primary endpoint was the proportion of patients with greater than 30% reduction from baseline in mean serum PTH during weeks 20-27. Key secondary endpoints included the proportion of patients with greater than 50% and greater than 30% reduction in PTH, and the mean weekly days of self-reported nausea and vomiting over the first eight weeks. The study found Parsabiv resulted in a higher proportion of patients reaching at least a 30% reduction in mean serum PTH during weeks 20-27 compared to baseline: 68.2% vs 57.7%, respectively (p=0.004). Significantly more Parsabiv patients also achieved greater than a 50% reduction from baseline in mean serum PTH during weeks 20-27: 52.4% vs 40.2%, respectively (p=0.001). The study met the primary endpoint and showed Parsabiv was non-inferior to oral Sensipar. Further, Parsabiv was superior to Sensipar for the secondary endpoints. Adverse events that were reported in greater than 10% of patients in either arm included blood calcium decreases, nausea, vomiting and diarrhea. Hypocalcemia (symptomatic) was reported in 5.0% of patients who received Parsabiv vs 2.3% in the Sensipar group.]


II. When Parsabiv (Etelcalcetide) is medically necessary, therapy will be initially approved for 6 months based on FDA approved recommendations

a. The recommended starting dose is 5 mg administered by intravenous bolus injection 3 times a week at the end of hemodialysis. Maintenance dose is individualized with a dose range of 2.5 to 15 mg three times per week.
III. Continuation of Parsabiv (etelcalcetide) dose between 2.5 to 15 mg IV will be approved annually at the FDA approved dose if the following criteria is met:
a. When member has greater than 30% reduction from baseline in mean Parathyroid hormone (PTH).

b. Member does not have unacceptable toxicity to Parsabiv.



[INFORMATIONAL NOTE: Unacceptable toxicity to Parsabiv includes severe hypocalcemia that may lead to QT interval prolongation ventricular arrhythmia and seizures. Others include worsening heart failure, and upper gastrointestinal bleeding. In clinical studies, two patients treated with Parsabiv in 1253 patient-years of exposure had upper gastrointestinal (GI) bleeding noted at the time of death while no patient in the control groups in 384 patient-years of exposure had upper GI bleeding noted at the time of death. The exact cause of GI bleeding in these patients is unknown and there were too few cases to determine whether the cases were related to Parsabiv]


IV. Parsabiv (etelcalcetide) for the treatment of other conditions/diseases is considered investigational.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specific to this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Etelcalcetide (Parsabiv)
Parsabiv (Etelcalcetide)

References:
1. Parsabiv (etelcalcetide) Prescribing information. Amgen. Thousand Oaks, CA. March 2019.

2. Geoffrey A, David AB et al. Effect of Etelcalcetide vs Placebo on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism. Two Randomized Clinical Trials. JAMA. 2017;317(2):146-155.

3. Medscape Medical News. Etelcalcetide Lowers PTH in Patients on Dialysis. Accessed February 28, 2017. Available at: http://www.medscape.com/viewarticle/874413?NO_BOXING=1

4. Utiger RD. Treatment of primary hyperparathyroidism. N Engl J Med 1999; 341:1301.

5. Sensipar (cinacalcet) Prescribing information. Amgen. Thousand Oaks, CA. August 2011.

6. Amgen News Releases. Study Results Published in the Journal of American Medical Association Show Amgen’s Parsabiv (Etelcalcetide) Significantly Reduced Serum Parathyroid Hormone in Adults With Secondary Hyperparathyroidism on Hemodialysis. Accessed January 25, 2018. Available at: https://www.amgen.com/media/news-releases/2017/01/study-results-published-in-the-journal-of-the-american-medical-association-show-amgens-parsabiv-etelcalcetide-significantly-reduced-serum-parathyroid-hormone-in-adults-with-secondary-hyperparathyroidism-on-hemodialysis/

7. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2009 Feb 29 - . Identifier NCT01896232, Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet; 2017 Feb 8 [cited 2018 Jan 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT01896232.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

J0606

* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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