Subject: Prolia 2026-A SGM P2021

Drug

PROLIA  (denosumab)

Policy:

I.    INDICATIONS 

The indications below including FDA-approved indications and compendial uses are considered a covered benefit provided that all the approval criteria are met and the member has no exclusions to the prescribed therapy. 

A.   FDA-Approved Indications
      1.   Treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of
            osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to
            other available osteoporosis therapy.
      2.   Treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of
            osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other
            available osteoporosis therapy.
      3.   Treatment of men and women with glucocorticoid-induced osteoporosis at high risk for fracture who are either
            initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of
            prednisone and expected to remain on glucocorticoids for at least 6 months.
      4.   Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy
            (ADT) for non-metastatic prostate cancer
      5.   Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor
            therapy for breast cancer
B.   Compendial Uses
      1.   Prevention or treatment of osteoporosis during androgen deprivation therapy for prostate cancer in patients
            with high fracture risk
      2.   Consider in postmenopausal patients receiving adjuvant aromatase inhibition therapy along with calcium and
            vitamin D supplementation to maintain or improve bone mineral density and reduce risk of fractures 

All other indications are considered experimental/investigational and not medically necessary. 

II.  DOCUMENTATION 

Submission of the following information is necessary to initiate the prior authorization review: Supporting chart notes or medical record indicating a history of fractures, T-score, and FRAX fracture probability as applicable to Sections III.A, III.B, and III.C. 

III. CRITERIA FOR INITIAL APPROVAL 

A.   Postmenopausal osteoporosis
      Authorization of 12 months may be granted to postmenopausal members with osteoporosis when ANY of
      the following criteria are met:
      1.   Member has a history of fragility fractures
      2.   Member has a pre-treatment T-score less than or equal to -2.5 OR member has osteopenia (i.e.,
            pre-treatment T-score greater than -2.5 and less than -1) with a high pre-treatment FRAX fracture
            probability (See Appendix B) and meets ANY of the following criteria:
            a.   Member has indicators of very high fracture risk (e.g., advanced age, frailty, glucocorticoid use, very
                  low T-scores [less than or equal to -3], or increased fall risk)
            b.   Member has failed prior treatment with or is intolerant to previous injectable osteoporosis therapy
                 (e.g., zoledronic acid [Reclast], teriparatide [Forteo, Bonsity], abaloparatide [Tymlos])
            c.   Member has had an oral bisphosphonate trial of at least 1-year duration or there is a clinical reason
                  to avoid treatment with an oral bisphosphonate (See Appendix A) 

B.   Osteoporosis in men
      Authorization of 12 months may be granted to male members with osteoporosis when ANY of the following
      criteria are met:
      1.   Member has a history of an osteoporotic vertebral or hip fracture¹⁰
      2.   Member meets BOTH of the following criteria:
            a.   Member has a pre-treatment T-score less than or equal to -2.5 OR member has osteopenia
                  (i.e., pre-treatment T-score greater than -2.5 and less than -1) with a high pre-treatment FRAX
                  fracture probability (See Appendix B)¹⁰
            b.   Member has had an oral OR injectable bisphosphonate trial of at least 1-year duration OR there is
                  a clinical reason to avoid treatment with a bisphosphonate (See Appendix A) 

C.   Glucocorticoid-induced osteoporosis
      Authorization of 12 months may be granted to members with glucocorticoid-induced osteoporosis when ALL
      of the following criteria are met:
      1.   Member is currently receiving or will be initiating glucocorticoid therapy at an equivalent prednisone dose
            of ≥ 2.5 mg/day for ≥ 3 months.
      2.   Member has had an oral OR injectable bisphosphonate trial of at least 1-year duration OR there is a clinical
            reason to avoid treatment with a bisphosphonate (See Appendix A)
      3.   Member meets ANY of the following criteria:
            a.   Member has a history of a fragility fracture
            b.   Member has a pre-treatment T-score less than or equal to -2.5
            c.   Member has osteopenia (i.e., pre-treatment T-score greater than -2.5 and less than -1) with a high
                 pre-treatment FRAX fracture probability (See Appendix B) 

D.   Breast cancer
      Authorization of 12 months may be granted to members who are receiving adjuvant aromatase inhibition
      therapy for breast cancer. 

E.   Prostate cancer
      Authorization of 12 months may be granted to members who are receiving androgen deprivation therapy for
      prostate cancer.

IV.  CONTINUATION OF THERAPY 

Authorization of 12 months may be granted for all members (including new members) who are currently receiving the requested medication through a previously authorized pharmacy or medical benefit, who meet one of the following:
1.   Member has received less than 24 months of therapy and has experienced clinical benefit (e.g., no new fracture
      seen on radiography) and has not experienced clinically significant adverse events during therapy.
2.   Member has experienced clinical benefit as evidenced by a bone mass measurement showing an improvement
      or stabilization in T-score compared with the previous bone mass measurement and member has not experienced
      any adverse effects.

Special Notes:

V.   APPENDIX
      Appendix A. Clinical reasons to avoid oral bisphosphonate therapy
      •   Presence of anatomic or functional esophageal abnormalities that might delay transit of the tablet
           (e.g., achalasia, stricture, or dysmotility)
      •   Active upper gastrointestinal problem (e.g., dysphagia, gastritis, duodenitis, erosive esophagitis, ulcers)
      •   Presence of documented or potential gastrointestinal malabsorption (e.g., gastric bypass procedures, celiac
           disease, Crohn’s disease, infiltrative disorders, etc.)
      •   Inability to stand or sit upright for at least 30 to 60 minutes
      •   Inability to take oral bisphosphonate at least 30 to 60 minutes before first food, drink, or medication of the day
      •   Renal insufficiency (creatinine clearance <35 mL/min)
      •   History of intolerance to an oral bisphosphonate 

Appendix B. WHO Fracture Risk Assessment Tool
•   High FRAX fracture probability: 10 year major osteoporotic fracture risk ≥ 20% or hip fracture risk ≥ 3%.
•   10-year probability; calculation tool available at: https://www.sheffield.ac.uk/FRAX/
•   The estimated risk score generated with FRAX should be multiplied by 1.15 for major osteoporotic fracture
     (including fractures of the spine (clinical), hip, wrist, or humerus) and 1.2 for hip fracture if glucocorticoid
     treatment is greater than 7.5 mg (prednisone equivalent) per day.

Place of Service:

Outpatient

The above policy is based on the following references:

1. Prolia [package insert]. Thousand Oaks, CA: Amgen Inc.; May 2021.
2. The NCCN Drugs & Biologics Compendium™ © 2020 National Comprehensive Cancer Network, Inc. http://www.nccn.org. Accessed October 13, 2020.
3. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO:  Wolters Kluwer Health Inc; October 24, 2019. Accessed October 13, 2021.
4. Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10): 2359-2381.
5. Jeremiah MP, Unwin BK, Greenwald MH, et al. Diagnosis and management of osteoporosis. Am Fam Physician. 2015;92(4):261-268.
6. 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 2020. Endocr Pract. 2020;26 (Suppl 1):1-46.
7. National Institute for Health and Care Excellence. Osteoporosis Overview. Last updated February 2018. Available at: http://pathways.nice.org.uk/pathways/osteoporosis. Accessed October 3, 2019.
8. Treatment to prevent osteoporotic fractures: an update. Department of Health and Human Services, Agency for Healthcare Research and Quality. 2012; Publication No. 12-EHC023-EF. Available at www.effectivehealthcare.ahrq.gov/lbd.cfm.
9. Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocr Metab. 2012;97(6):1802-1822.
10. Gralow JR, Biermann S, Farooki A, et al. NCCN Task Force Report: Bone Health in Cancer Care. JNCCN. 2013; 11(Suppl 3):S1-50.
11. FRAX® Fracture Risk Assessment Tool. © Centre for Metabolic Bone Diseases, University of Sheffield, UK. Available at: https://www.shef.ac.uk/FRAX. Accessed October 13,2021.
12. Fink HA, Gordon G, Buckley L, et al. 2017 American College of Rheumatology Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res. 2017;69:1521-1537.
13. Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med 2017;167(03):ITC17–ITC32.
14. Eastell R, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2019;104:1595-1622.
15. Carey John. What is a ‘failure’ of bisphosphonate therapy for osteoporosis? Cleveland Clinic Journal of Medicine Nov 2005, 72 (11) 1033-1039.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

April 17, 2022