(burosumab-twza)

Last Review Date: 05/02/2022

Date of Origin: 05/01/2018

Dates Reviewed: 05/2018, 05/2019, 11/2019, 05/2020, 07/2020, 05/2021, 05/2022

1. Length of Authorization

Initial coverage will be provided for 6 months and may be renewed every 12 months thereafter.

2. Dosing Limits

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

• Crysvita 10 mg/mL vial: 1 vial every 14 days
• Crysvita 20 mg/mL vial: 1 vial every 14 days
• Crysvita 30 mg/mL vial: 6 vials every 14 days

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

• XLH

• 90 billable units every 14 days (pediatrics)
• 90 billable units every 28 days (adults)

• TIO

• 180 billable units every 14 days

3. Initial Approval Criteria^{1,2,3,4,5,6,7,8}

Coverage is provided in the following conditions:

• Patient has not received oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol) within 1 week prior to the start of therapy; AND
• Baseline fasting serum phosphorus* level with current hypophosphatemia, defined as a phosphate level below the lower limit of the laboratory normal reference range (Note: serum phosphorus levels should be monitored periodically throughout therapy, required on renewal); AND
• Patient has a reduced tubular resorption of phosphate corrected for glomerular filtration rate (TmP/GFR); AND
• Other causes of hypophosphatemia (e.g., autosomal dominant or recessive hypophosphatemic rickets) have been ruled out; AND

Universal Criteria

• Must be prescribed by, or in consultation with, a nephrologist or endocrinologist; AND
• Will not be used concomitantly with oral phosphate and/or active vitamin D analogs (e.g., calcitriol, paricalcitol, doxercalciferol, calcifediol); AND
• Patient does not have severe renal impairment, defined as a glomerular filtration rate (GFR) of <30 mL/min; AND
• Patient 25-hydroxy vitamin D levels will be monitored at baseline and intermittently and patient will be supplemented with cholecalciferol or ergocalciferol to maintain levels in the normal range for age; AND

X-linked Hypophosphatemia (XLH) † Ф

• Patient is at least 6 months of age; AND
• Diagnosis is confirmed by identifying at least one of the following:
  • Serum fibroblast growth factor-23 (FGF23) level > 30 pg/mL (>230 RU/mL in children 3 months-17 years; >180 RU/mL in adults using EDTA plasma); OR
  • Phosphate regulating gene with homology to endopeptidases located on the X chromosome (PHEX-gene) mutations in the patient; AND

• Adult patients must have had an inadequate response from oral phosphate and active vitamin D analogs

Tumor-induced Osteomalacia (TIO) † Ф

• Patient is at least 2 years of age; AND
• Must have a diagnosis of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized; AND

• Diagnosis is confirmed by identifying excessive FGF23 (i.e., level ≥ 100 pg/mL) that is not amenable to cure by surgical excision of the offending tumor/lesion.

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

*Note: Phosphorous levels should be obtained fasting 12 hours or more without food or drink except for water and after an adequate washout period after supplements; lab values (i.e. GFR, phosphorous, TmP/GFR) should be obtained within 28 days of the date of administration.

4. Renewal Criteria^1,2,3

Authorizations can be renewed based on the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria as identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: severe hypersensitivity reactions, hyperphosphatemia and/or nephrocalcinosis, severe injection site reactions, etc.; AND
• Current serum phosphorus level is not above the upper limit of the laboratory normal reference range; AND
• Disease response as indicated by increased serum phosphorus levels, a reduction in serum total alkaline phosphatase activity, improvement in symptoms (e.g., skeletal pain, linear growth, etc.), and/or improvement in radiographic imaging of Rickets/osteomalacia; AND
• Pediatric patients must be re-evaluated at adulthood or upon closure of bony epiphyses (whichever occurs first) in order to determine if continued therapy is necessary (i.e., discontinuation of burosumab in order to reassess whether treatment with oral phosphate and active vitamin D analogs provide an adequate response); AND
• (Tumor-Induced Osteomalacia only): If a patient undergoes treatment of the underlying tumor (i.e., surgical excision or radiation therapy) treatment should be interrupted and serum phosphorus reassessed after treatment has been completed.

5. Dosage/Administration¹

6. Billing Code/Availability Information

HCPCS code:

• J0584 - Injection, burosumab-twza 1 mg; 1 billable unit = 1 mg

NDC:

• Crysvita 10 mg/mL single-dose vial: 69794-0102-xx
• Crysvita 20 mg/mL single-dose vial: 69794-0203-xx
• Crysvita 30 mg/mL single-dose vial: 69794-0304-xx

7. References

1. Crysvita [package insert]. Novato, CA; Ultragenyx, Pharm.; June 2020. Accessed March 2022.
2. Whyte MP, Portale A, Imel E, Boot A, Hogler W, et al. Burosumab (KRN23), a fully human anti-FGF23 monoclonal antibody for X-linked hypophosphatemia (XLH): final 64-week results of a randomized, open-label, phase 2 study of 52 children (meeting abstract). J Bone Miner Res. 2017;32(S1)
3. Imel E, Carpenter T, Gottesman GC, et al. The effect of burosumab (KRN23), a fully human anti-FGF23 monoclonal antibody, on phosphate metabolism and rickets in 1 to 4-year-old children with X-linked hypophosphatemia (XLH). (Meeting abstract). J Bone Miner Res. 2017;32(S1)
4. Ruppe MD. X-Linked Hypophosphatemia. 2012 Feb 9 [Updated 2017 Apr 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.  Available from: https://www.ncbi.nlm.nih.gov/books/NBK83985/ 
5. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood.  Endocr Connect. 2014 Mar 1; 3(1): R13–R30.
6. Carpenter TO, Imel EA, Holm IA, et al. A clinician's guide to x-linked hypophosphatemia.  J Bone Miner Res. 2011 Jul; 26(7): 1381–1388.
7. Felsenfeld AJ, Levine BS. Approach to treatment of hypophosphatemia. Am J Kidney Dis. 2012 Oct;60(4):655-61.
8. Chong W, Molinolo A, Chen C, et al. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011 Jun; 18(3): R53–R77. Published online 2011 Jun 8. doi: 10.1530/ERC-11-0006

Appendix 1 – Covered Diagnosis Codes

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

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 Determination (NCD), Local Coverage Articles (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/ search.aspx. Additional indications may be covered at the discretion of the health plan.

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