Last Review Date: 04/04/2024

Date of Origin: 11/28/2011

Dates Reviewed: 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 01/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 06/2018, 04/2019, 04/2020, 04/2021, 04/2022, 04/2023, 10/2023, 04/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Prolia & Jubbonti: 60 mg/1 mL single-dose prefilled syringe: 1 syringe every 6 months
• Xgeva & Wyost: 120 mg/1.7 mL single-dose vial:
  • Load: 4 vials for one 29-day cycle
  • Maintenance: 1 vial monthly

B. Max Units (per dose and over time) [HCPCS Unit]:

3. Initial Approval Criteria

Prolia & Jubbonti

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ^1,2,31,35

• Patient must be supplementing with 1,000 mg of calcium and at least 400 IU of vitamin D daily; AND
• Patient must not have hypocalcemia; AND
• Patients with advanced kidney disease (i.e., eGFR < 30 mL/min/1.73 m² and including dialysis-dependent patients) will be monitored for the presence of chronic kidney disease- mineral and bone disorder (CKD-MBD) with intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25 (OH)₂ vitamin D prior to decisions regarding denosumab treatment; AND
• Pregnancy is ruled out prior to administration in biologic females of child-bearing potential; AND
• Will not be used in combination with other denosumab products, bisphosphonates, romosozumab, or parathyroid hormone analogs/related peptides; AND

Osteoporosis in Men and Women † ^{1,2,28,29,31,33,35}

• Biological female patient must be post-menopausal; AND
• Patient must be at a high risk for fracture**; AND
• Patient has a documented diagnosis of osteoporosis indicated by one or more of the following:
  • T-score by DXA of ≤-2.5 measured at the lumbar spine, femoral neck, total hip, or forearm at the 33% (one-third) radius site; OR
  • History of fragility fracture to the hip or spine, regardless of T-score; OR
  • T-score by DXA between -1.0 and -2.5 measured at the lumbar spine, femoral neck, total hip, or forearm at the 33% (one-third) radius site; AND
    • History of fracture of proximal humerus, pelvis, or distal forearm; OR
    • FRAX 10-year probability for major fracture ≥ 20% or hip fracture ≥ 3%; AND
• Patient has one of the following:
  • Documented treatment failure or ineffective response^± to a minimum (12) month trial on previous therapy with bisphosphonates (oral or IV) such as alendronate, risedronate, ibandronate, or zoledronic acid; OR
  • Patient has a documented contraindication* or intolerance to BOTH oral bisphosphonates AND intravenous (IV) bisphosphonates such as alendronate, risedronate, ibandronate, or zoledronic acid

Glucocorticoid-Induced Osteoporosis † ‡ ^1,2,21,37

• Patient will be initiating or is continuing systemic glucocorticoid therapy at a daily dosage equivalent to ≥ 2.5 mg of prednisone and is expected to remain on glucocorticoid therapy for at least 3 months; AND
• Patient must be at an increased risk for fracture ¥; AND
  • Documented treatment failure or ineffective response^± to a minimum (12) month trial on previous therapy with bisphosphonates (oral or IV) such as alendronate, risedronate, ibandronate, or zoledronic acid; OR
  • Patient has a documented contraindication* or intolerance to BOTH oral bisphosphonates AND intravenous (IV) bisphosphonates such as alendronate, risedronate, ibandronate, or zoledronic acid

Osteoporosis treatment and prevention in prostate cancer patients † ‡ ^1,2,5,22,38

• Patient must be receiving androgen deprivation therapy; AND
• Patient must be at a high risk for fracture**

Osteoporosis treatment and prevention in breast cancer patients † ‡ ^1,2,5,23,39

• Patient must be receiving adjuvant aromatase inhibitor therapy for breast cancer

    Xgeva & Wyost

Coverage is provided in the following conditions:

Universal Criteria ^{3,4,34,35,38,39}

• Patient will receive calcium and vitamin D as necessary to treat or prevent hypocalcemia (Note: excludes when use is for hypercalcemia of malignancy); AND
• Patient must not have hypocalcemia; AND
• Will not be used in combination with other denosumab products, bisphosphonates, romosozumab, or parathyroid hormone analogs/related peptides; AND

Prevention of skeletal-related events in patients with multiple myeloma OR bone metastases from solid tumors † ^{3-5,16-18,25,27,38,39}

• Patient is at least 18 years of age; AND

• Patient must try and have an inadequate response, contraindication*, or intolerance to at least a three (3) month trial of zoledronic acid; OR
• Patient has metastatic breast cancer, metastatic castration-resistant prostate cancer, or metastatic lung cancer (both SCLC and NSCLC)

Giant Cell Tumor of the Bone † Ф ^3-5,7,25,26

• Patient must be an adult or at least 12 years of age and skeletally mature; AND
  • Disease is unresectable or surgical resection is likely to result in severe morbidity; OR
  • Disease is localized, recurrent, or metastatic ‡; AND
    • Used as a single agent; OR
    • Used in combination with serial embolization and/or radiation therapy

Hypercalcemia of malignancy † Ф ^3-5,11

• Patient is at least 18 years of age; AND
• Patient must have a diagnosis of cancer (malignancy); AND
  • Patient must have a diagnosis of refractory hypercalcemia of malignancy defined as an albumin-corrected calcium of >12.5 mg/dL (3.1 mmol/L) despite treatment with a minimum seven (7) day trial on previous therapy with intravenous (IV) bisphosphonates such as ibandronate or zoledronic acid; OR
  • Patient has a documented contraindication* or intolerance to intravenous (IV) bisphosphonates such as ibandronate or zoledronic acid

Systemic Mastocytosis ‡ ^5,30

• Patient has osteopenia or osteoporosis and coexisting bone pain; AND
  • Used as second line therapy if patient is not responding to bisphosphonate therapy; OR
  • Patient is not a candidate for bisphosphonate therapy due to renal insufficiency

      † FDA Approved Indication(s); ‡ Compendia recommended indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-4

Coverage can be renewed based on the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe symptomatic hypocalcemia, osteonecrosis of the jaw, atypical femoral fractures, dermatological adverse reactions, severe infection, severe hypersensitivity/anaphylaxis, musculoskeletal pain, etc.; AND

Prolia & Jubbonti ^{1,2,5,28,29,33,37-39}

• Beneficial disease response as indicated by one or more of the following:
  • Absence of fractures
  • Increase in bone mineral density compared to pretreatment baseline; AND

Osteoporosis in Men and Women:

• • After 5 years of treatment, patient will have a repeat DXA performed; AND
  • Patients with low-to moderate risk disease will have therapy changed to an oral or IV bisphosphonate unless there is a contraindication or intolerance to both dosage forms

Glucocorticoid-Induced Osteoporosis:

• • After 2 years of treatment, patient will have a repeat DXA performed; AND
  • Patients with low-to moderate risk disease will have therapy changed to an oral or IV bisphosphonate unless there is a contraindication or intolerance to both dosage forms

Xgeva & Wyost ^3-5,26,38,39

• Beneficial disease response as indicated by the following:
  • Multiple Myeloma OR Bone metastases from solid tumors: absence/delay in skeletal-related events (e.g., pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression)
  • Giant Cell Tumor of the Bone: stabilization of disease or decrease in size of tumor or spread of tumor
  • Hypercalcemia of Malignancy: corrected serum calcium ≤ 11.5 mg/dL (2.9 mmol/L)
  • Systemic Mastocytosis: improvement or resolution of bone pain as compared to pretreatment baseline

5. Dosage/Administration ^1-4

Prolia & Jubbonti

Xgeva & Wyost

6. Billing Code/Availability Information

HCPCS Code(s):

Prolia & Xgeva

• J0897 – Injection, denosumab, 1 mg; 1 mg = 1 billable unit

Jubbonti & Wyost

• J3590 – Unclassified biologics (Discontinue use on 10/01/2024)
• Q5136 – Injection, denosumab-bbdz (jubbonti/wyost), biosimilar, 1 mg; 1 billable unit = 1 mg (Effective 10/01/2024)

NDC(s):

• Prolia 60 mg/1 mL single-dose prefilled syringe: 55513-0710-xx
• Jubbonti 60 mg/1 mL single-dose prefilled syringe: 61314-0240-xx
• Xgeva 120 mg/1.7 mL single-dose vial: 55513-0730-xx
• Wyost 120 mg/1.7 mL single-dose vial: 61314-0228-xx

7. References

1. Prolia [package insert]. Thousand Oaks, CA; Amgen, Inc.; March 2024. Accessed March 2024.
2. Jubbonti [package insert]. Princeton, NJ; Sandoz, Inc.; March 2024. Accessed March 2024.
3. Xgeva [package insert]. Thousand Oaks, CA; Amgen, Inc.; June 2020. Accessed March 2024.
4. Wyost [package insert]. Princeton, NJ; Sandoz, Inc.; March 2024. Accessed March 2024.
5. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Denosumab. National Comprehensive Cancer Network, 2024.  The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
6. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15;18(16):4415-24.
7. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumor of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275-80.
8. WHO Scientific Group on the Prevention and Management of Osteoporosis. Prevention and management of osteoporosis: report of a WHO scientific group. (WHO technical report series; 921). Geneva, Switzerland: WHO; 2000.
9. Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary health care level. Technical Report. World Health Organization Collaborating Center for Metabolic Bone Diseases. University of Sheffield, UK; 2007.
10. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014.
11. Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab. 2014 Sep;99(9):3144-52. doi: 10.1210/jc.2014-1001. Epub 2014 Jun 10.
12. Camacho PM, Petak SM, Binkley N, et al. American Association Of Clinical Endocrinologists And American College Of Endocrinology Clinical Practice Guidelines For The Diagnosis And Treatment Of Postmenopausal Osteoporosis - 2016. Endocr Pract. 2016 Sep 2; 22(Suppl 4):1-42.
13. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomized, double-blind, placebo-controlled trial. Lancet. 2015 Aug 1;386(9992):433-43.
14. Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians. Ann Intern Med. 2017 May 9. doi: 10.7326/M15-1361.
15. Jeremiah MP, Unwin BK, Greenawald MH, et al. Diagnosis and Management of Osteoporosis. Am Fam Physician. 2015 Aug 15;92(4):261-8.
16. Henry DH, Costa L, Goldwasser F, et al. Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma. Journal of Clinical Oncology 2011 29:9, 1125-1132. 2011 Mar 20.
17. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010 Dec 10;28(35):5132-9.
18. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. Lancet. 2011 Mar 5;377(9768):813-22.
19. Cummings SR, San Martin J, McClung MR, et al. Denosumab for Prevention of Fractures in Postmenopausal Women With Osteoporosis. N Engl J Med, 361 (8), 756-65; 2009 Aug 20. PMID: 19671655. DOI: 10.1056/NEJMoa0809493.
20. Orwoll E, Teglbjaerg CS, Langdahl BL, et al. A Randomized, Placebo-Controlled Study of the Effects of Denosumab for the Treatment of Men With Low Bone Mineral Density. J Clin Endocrinol Metab, 97 (9), 3161-9; Sept 2012. PMID: 22723310. DOI: 10.1210/jc.2012-1569. 
21. Saag KG, Wagman RB, Geusens P, et al. Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: A Multicentre, Randomized, Double-Blind, Active-Controlled, Double-Dummy, Non-Inferiority Study. Lancet Diabetes Endocrinol, 6 (6), 445-454; Jun 2018. PMID: 29631782. DOI: 10.1016/S2213-8587(18)30075-5.
22. Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer. N Engl J Med. 2009 Aug 20; 361(8): 745-755.
23. Ellis GK, Bone HG, Chlebowski R, et al. Randomized Trial of Denosumab in Patients Receiving Adjuvant Aromatase Inhibitors for Nonmetastatic Breast Cancer. J Clin Oncol, 26 (30), 4875-82; 2008 Oct 20. PMID: 18725648. DOI: 10.1200/JCO.2008.16.3832.
24. Raje N, Terpos E, Willenbacher W, et al. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Double-Dummy, Randomized, Controlled, Phase 3 Study. Lancet Oncol, 19 (3), 370-381; Mar 2018. PMID: 29429912. DOI: 10.1016/S1470-2045(18)30072-X.
25. Chawla S, Henshaw R, Seeger L, et al. Safety and Efficacy of Denosumab for Adults and Skeletally Mature Adolescents With Giant Cell Tumour of Bone: Interim Analysis of an Open-Label, Parallel-Group, Phase 2 Study. Lancet Oncol, 14 (9), 901-8; Aug 2013. PMID: 23867211. DOI: 10.1016/S1470-2045(13)70277-8.
26. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Bone Cancer. Version 1.2024.  National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
27. Scagliotti GV, Hirsh V, Siena S, et al. Overall Survival Improvement in Patients With Lung Cancer and Bone Metastases Treated With Denosumab Versus Zoledronic Acid: Subgroup Analysis From a Randomized Phase 3 Study. J Thorac Oncol, 7 (12), 1823-1829; Dec 2012. PMID: 23154554. DOI: 10.1097/JTO.0b013e31826aec2b.
28. Eastell R, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 5, May 2019, Pages 1595–1622, https://doi.org/10.1210/jc.2019-00221. Published: 25 March 2019.
29. Shoback D, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. Doi: 10.1210/clinem/dgaa048.
30. Orsolini G, Gavioli I, Tripi G, et al. Denosumab for the Treatment of Mastocytosis-Related Osteoporosis: A Case Series. Calcif Tissue Int. 2017 Jun;100(6):595-598. doi: 10.1007/s00223-017-0241-z.
31. Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. Menopause. 2021 Sep 1;28(9):973-997. Doi: 10.1097/GME.0000000000001831.
32. Rosen HN. (2023). Bisphosphonate therapy for the treatment of osteoporosis. In Rosen CJ, Schmader KE (Eds.), UptoDate. Last updated: May 03, 2023. Accessed March 7, 2024. Available from https://www.uptodate.com/contents/bisphosphonate-therapy-for-the-treatment-of-osteoporosis?sectionName=Contraindications%20to%20bisphosphonates&search=postmenopausal%20osteoporosis&topicRef=2064&anchor=H3422893804&source=see_link#H3422893804
33. Camacho PM, Petak SM, Binkley N, et al. American Association Of Clinical Endocrinologists/American College Of Endocrinology Clinical Practice Guidelines For The Diagnosis And Treatment Of Postmenopausal Osteoporosis-2020 Update. Endocr Pract. 2020 May;26(Suppl 1):1-46. doi: 10.4158/GL-2020-0524SUPPL.
34. Jackson RD, LaCroix AZ, Gass M, Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006; 354(7):669–683.
35. LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-2102. Doi: 10.1007/s00198-021-05900-y. Epub 2022 Apr 28.
36. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al; Clinical Guidelines Committee of the American College of Physicians. Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. Ann Intern Med. [Epub 3 January 2023]. doi:10.7326/M22-1034.
37. Humphrey, M.B., Russell, L., Danila, M.I., et al. (2023), 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol, 75: 2088-2102. https://doi.org/10.1002/art.42646
38. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Prostate Cancer. Version 3.2024.  National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
39. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Breast Cancer. Version 2.2024.  National Comprehensive Cancer Network, 2024. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc.” To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed March 2024.
40. National Government Services, Inc. Local Coverage Article: Billing and Coding: Denosumab (Prolia ™, Xgeva ™) (A52399). Centers for Medicare & Medicaid Services, Inc.  Updated on 12/15/2023 with effective date 12/21/2023. Accessed March 2024.

Appendix 1 – Covered Diagnosis Codes

      Prolia & Jubbonti

Xgeva & Wyost

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/Article):

Prolia and Xgeva