CurrentCentenePolicy N/A

Clinical Policy: Burosumab-twza (Crysvita)

Defines medical necessity criteria, dosing limits, approval durations, continued therapy requirements, exclusions, and coding implications for burosumab-twza (Crysvita) for X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) across Commercial, HIM and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyClinical Policy: Burosumab-twza (Crysvita)

Policy CodePolicy N/A

Change TypeMultiple annual reviews; material changes in 2022, 2024, 2025

Effective DateSep 1, 2018

Next Review Date

Key ActionProvider must submit office chart notes, labs (including current serum phosphorus within 30 days and FGF23 or genetic testing as applicable), and documentation of current weight to support that member meets all approval criteria.

POLICY UPDATE CHANGES

3Q 2024 annual review: added requirement to Continued Therapy that Crysvita not be used concomitantly with oral phosphate or vitamin D replacement therapy for all indications.

3Q 2025 annual review: for XLH, modified diagnostic confirmation to allow PHEX gene mutation in member or first-degree relative and added requirement for documentation of current weight; added step therapy bypass for IL HIM per IL HB 5395.

3Q 2022 annual review: for TIO added requirement for documentation of member's current weight for dose calculation purposes.

Multiple annual reviews (2021, 2022, 2023) noted 'no significant changes' except template and reference updates.

2Covered Indications

3Approval Durations (Commercial/Medicaid/HIM)

Coverage Summary

Burosumab-twza (Crysvita) is covered with criteria aligned to the FDA-approved indications: for X-linked hypophosphatemia (XLH) in patients aged 6 months and older and for FGF23-related tumor-induced osteomalacia (TIO) in patients aged 2 years and older. Coverage requires specialist involvement (prescribed by or in consultation with an endocrinologist or metabolic disease specialist), laboratory confirmation of diagnosis (e.g., elevated serum FGF23 or PHEX genetic testing where applicable), and documentation of current weight for dose calculation. Continued therapy criteria and dosing limits follow the policy's FDA-aligned indications and requirements.

Thresholds & Quick Facts

Serum phosphorus thresholdBelow age- and gender-specific laboratory reference range (use lab-specific ranges if available; otherwise Appendix D). Continued therapy: increase from baseline and/or maintenance within normal range without exceeding upper limit.

Dose limits - Pediatric XLHUp to 2 mg/kg, maximum 90 mg every two weeks.

Dose limits - Adult XLHUp to 1 mg/kg, maximum 90 mg every four weeks.

Dose limits - TIOUp to 2 mg/kg, maximum 180 mg every two weeks.

Covered indications (count)2 (X-linked hypophosphatemia [XLH]; Tumor-induced osteomalacia [TIO]).

Approval durations (Commercial / Medicaid / HIM)Initial: Commercial 6 months or to member renewal date; Medicaid/HIM 6 months. Continued therapy: Commercial 6 months or to renewal date; Medicaid/HIM 12 months.

HCPCS product codeJ0584 — Injection, burosumab-twza, 1 mg.

Initial Therapy Criteria

Initial Approval Criteria - X-linked hypophosphatemia (XLH)

Crysvita is medically necessary when ALL of the following are met:

ALL of the following

ONE of
- DNA testing confirms the presence of mutations in the PHEX gene in member or first-degree relative
- Elevated serum FGF23 levels
Prescribed by or in consultation with an endocrinologist or metabolic disease specialist
Current (within the last 30 days) serum phosphorus level is either below the reference range for age/gender (use lab-specific ranges if available; otherwise Appendix D) AND member has not received oral phosphate or vitamin D replacement therapy; OR serum phosphorus is within the normal range but member remains symptomatic (e.g., rickets, growth impairment, musculoskeletal pain, bone fractures) despite currently receiving oral phosphate and/or vitamin D replacement therapy

Continuation Therapy Criteria

Continued Therapy - X-linked hypophosphatemia (XLH)

Members must meet the following to continue therapy:

ALL of the following

ONE of
- Member is currently receiving medication via Centene benefit
- Member has previously met initial approval criteria
ALL of the following
- An increase in serum phosphorus from baseline and/or maintenance within the normal range for age and gender; not to exceed the upper limit of that normal range (use lab-specific reference ranges if available; otherwise Appendix D)See Appendix D lab-specific ranges

Other Diagnoses & Exclusions

Other diagnoses/indications

If not specifically listed above, coverage follows formulary/off-label/non-formulary policies:

ANY of the following

For drugs on formulary/PDL: follow no coverage criteria policy for relevant line of business (CP.CPA.190 commercial; HIM.PA.33 marketplace; CP.PMN.255 Medicaid)
For drugs NOT on formulary/PDL: follow non-formulary policy for relevant line of business (CP.CPA.190 commercial; HIM.PA.103 marketplace; CP.PMN.16 Medicaid)
If requested use is not listed under section III and criterion 1 does not apply, refer to off-label use policy for relevant line of business (CP.CPA.09 commercial; HIM.PA.154 marketplace; CP.PMN.53 Medicaid)

Diagnoses/Indications Not Authorized

Provider Actions

Prior Authorization

Submit clinical documentation for approval

Submit office chart notes, laboratory results, and documentation of current weight to support that the member meets all approval criteria. Required laboratory documentation includes a current serum phosphorus obtained within the last 30 days and FGF23 testing or genetic testing as applicable. Affected code: J0584.

Office chart notes
Labs including current serum phosphorus within 30 days
FGF23 or genetic testing (as applicable)
Documentation of current weight

Documentation Required

Confirm diagnostic testing

For XLH: provide diagnostic confirmation with either DNA testing showing a PHEX gene mutation in the member or a first-degree relative, OR elevated serum FGF23 levels. For TIO: provide documentation of elevated serum FGF23 and documentation that the causative tumor(s) is/are not amenable to surgical excision or resection (unresectable or not localized).

Applicable Codes

HCPCS - ProductHCPCSCovered

J0584

Injection, burosumab-twza, 1 mg

Product Availabilitymixed

N/A	Single-dose vials for injection: 10 mg/mL, 20 mg/mL, 30 mg/mL

Clinical Evidence & References

Evidence and guidance sources referenced in this policy include the Crysvita Prescribing Information (Kyowa Kirin, March 2023; accessed 2025-04-11) and peer-reviewed clinical practice recommendations such as the 2019 Nature Reviews Nephrology guidance for XLH, along with additional cited literature on diagnosis and management of XLH and TIO summarized in the policy references.

Background

Burosumab-twza (Crysvita) is an FGF23-blocking monoclonal antibody. The FDA-approved indications are X-linked hypophosphatemia (XLH) for patients aged 6 months and older and FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) for patients aged 2 years and older. This policy aligns coverage to those FDA indications and requires prescribing by or in consultation with an endocrinologist or metabolic disease specialist, laboratory confirmation of diagnosis (e.g., elevated serum FGF23 or PHEX genetic testing), prohibition of concurrent oral phosphate or active vitamin D analog therapy (contraindicated), and documentation of current weight to support dose calculations and adherence to the policy's dosing thresholds.

Definitions

XLHX-linked hypophosphatemia; inherited disorder causing hypophosphatemia due to excess FGF23 activity.

TIOTumor-induced osteomalacia; FGF23-related hypophosphatemia from phosphaturic tumors not amenable to curative resection or localization.

FGF23Fibroblast growth factor 23; a hormone that regulates phosphate homeostasis and is targeted by burosumab.

Revision History

05.10.24material_change

3Q 2024 annual review: added requirement to Continued Therapy that Crysvita not be used concomitantly with oral phosphate or vitamin D replacement therapy for all indications (P&T Approval Date 08.24).

06.26.25material_changeLatest

3Q 2025 annual review: for XLH, modified diagnostic confirmation to allow PHEX gene mutation in member or first‑degree relative and added requirement for documentation of current weight for dose calculation; added step therapy bypass for IL HIM per IL HB 5395 (P&T Approval Date 08.25).

05.12.22material_change

Policy Summary

PayerCentene

PolicyClinical Policy: Burosumab-twza (Crysvita)

Policy CodePolicy N/A

Change TypeMultiple annual reviews; material changes in 2022, 2024, 2025

Effective DateSep 1, 2018

Next Review Date

On This Page

See Appendix D lab-specific ranges

Use laboratory-specific reference ranges if available; otherwise refer to Appendix D

Crysvita is NOT prescribed concurrently with oral phosphate or vitamin D replacement therapy

Concomitant use is contraindicated per Appendix C

Documentation of member's current weight for dose calculation purposes

ALL of the following

Age 6 months to 18 years: 2 mg/kg up to 90 mg every two weeksMaximum 90 mg every 2 weeks
Age ≥ 18 years: 1 mg/kg up to 90 mg every four weeksMaximum 90 mg every 4 weeks

Initial Approval Criteria - Tumor-Induced Osteomalacia (TIO)

Crysvita is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of TIO with confirmed elevated serum FGF23 levels
Prescribed by or in consultation with an endocrinologist or metabolic disease specialist
Failure of a ≥ 3 consecutive month trial of oral phosphate and vitamin D replacement unless contraindicated or clinically significant adverse effects experienced3 months
If member has not received oral phosphate or vitamin D replacement therapy, see serum phosphorus criterion
Current (within the last 30 days) serum phosphorus level is either below the reference range for age/gender (use lab-specific ranges if available; otherwise Appendix D) AND member has not received oral phosphate or vitamin D replacement therapy; OR serum phosphorus is within the normal range but member remains symptomatic (e.g., osteomalacia, muscle weakness, fatigue, bone pain, fractures) despite currently receiving oral phosphate and/or vitamin D replacement therapySee Appendix D lab-specific ranges
Use laboratory-specific reference ranges if available; otherwise refer to Appendix D
Crysvita is NOT prescribed concurrently with oral phosphate or vitamin D replacement therapy
Concomitant use is contraindicated per Appendix C
Documentation confirms that the causative tumor(s) is/are not amenable to surgical excision or resection (cannot be curatively resected or localized)
Documentation of member's current weight for dose calculation purposes
Dose does not exceed 2 mg/kg (maximum 180 mg) every two weeksMaximum 180 mg every 2 weeks

Initial Approval Duration

ANY of the following

Medicaid/HIM: 6 months6 months
Commercial: 6 months or to the member's renewal date, whichever is longer6 months or to renewal date

A positive clinical response including any of: enhanced height velocity, improvement in skeletal deformities, reduction of fractures, reduction of generalized bone pain

Crysvita is NOT prescribed concurrently with oral phosphate or vitamin D replacement therapy

Documentation of member's current weight for dose calculation purposes

ALL of the following

Age 6 months to 18 years: 2 mg/kg up to 90 mg every two weeksMaximum 90 mg every 2 weeks
Age ≥ 18 years: 1 mg/kg up to 90 mg every four weeksMaximum 90 mg every 4 weeks

Continued Therapy - Tumor-Induced Osteomalacia (TIO)

Members must meet the following to continue therapy:

ALL of the following

ONE of
- Member is currently receiving medication via Centene benefit
- Member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state addendums CCPHARM.03A and CC.PHARM.03B)
ALL of the following
- An increase in serum phosphorus from baseline and/or maintenance within the normal range for age and gender; not to exceed the upper limit of that normal range (use laboratory-specific reference ranges if available; otherwise Appendix D)See Appendix D lab-specific ranges
- Documentation confirms improvement in symptoms (osteomalacia, muscle weakness, fatigue, bone pain, fractures)
Crysvita is NOT prescribed concurrently with oral phosphate or vitamin D replacement therapy
Documentation of member's current weight for dose calculation purposes
If request is for a dose increase, new dose does not exceed 2 mg/kg (maximum 180 mg)Maximum 180 mg every 2 weeks

Continued Therapy Duration

ANY of the following

Medicaid/HIM: 12 months12 months
Commercial: 6 months or to the member's renewal date, whichever is longer6 months or to renewal date

Non-FDA approved indications not addressed in this policy are not covered unless sufficient documentation per off-label use policies is provided

Refer to CP.CPA.09 (commercial); HIM.PA.154 (HIM); CP.PMN.53 (Medicaid)

Billing Rule

Dose and weight documentation

Document the member's current weight for dose calculation and ensure administered dose does not exceed the mg/kg limits and total mg caps per indication. For XLH: pediatric dosing up to 2 mg/kg (maximum 90 mg) every two weeks; adult dosing up to 1 mg/kg (maximum 90 mg) every four weeks. For TIO: dosing does not exceed 2 mg/kg (maximum 180 mg) every two weeks. Affected code: J0584.

Document current weight for dose calculation
XLH pediatric: up to 2 mg/kg, max 90 mg every 2 weeks
XLH adult: up to 1 mg/kg, max 90 mg every 4 weeks
TIO: up to 2 mg/kg, max 180 mg every 2 weeks

Denial Risk

Concurrent oral phosphate or active vitamin D use

Requests may be denied if Crysvita is prescribed concurrently with oral phosphate or active vitamin D analogs; concomitant use is contraindicated and is listed as a contraindication in the policy.

3Q 2022 annual review: for TIO added requirement for documentation of member's current weight for dose calculation purposes (P&T Approval Date 08.22).

05.10.21annual_review

3Q 2021 annual review: no significant changes; template and reference updates (Date 05.10.21, P&T Approval Date 08.21).

05.12.22annual_review

3Q 2022 annual review: no significant changes overall; references reviewed and updated (Date 05.12.22, P&T Approval Date 08.22).

04.07.23annual_review

3Q 2023 annual review: no significant changes; references reviewed and updated (Date 04.07.23, P&T Approval Date 08.23).