ModifiedUnitedHealthcarePolicy IEXD0068.11

Denosumab (brand and biosimilar) coverage

Medical benefit coverage and prior authorization criteria for denosumab products (Prolia, Xgeva, Jubbonti, Wyost) for multiple indications including osteoporosis, cancer-related bone disease, giant cell tumor, and hypercalcemia of malignancy; applies to UnitedHealthcare members per policy.

Policy Summary

PayerUnitedHealthcare

PolicyDenosumab (brand and biosimilar) coverage

Policy CodePolicy IEXD0068.11

Change TypeProduct list updateReview at Launch addedindication clarifications

Effective DateApr 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization (initial approvals limited to 12 months) and document diagnosis, risk status, and prior bisphosphonate failure or intolerance when required.

SourceLink

POLICY UPDATE CHANGES

Title changed from 'Denosumab (Prolia ® & Xgeva ® ) Coverage Rationale' and updated list of applicable denosumab products to include Jubbonti and Wyost.

Language indicating Jubbonti and Wyost have been added to the Review at Launch program; some members may not be eligible for coverage at this time.

Specified indications for Jubbonti (denosumab-bbdz) as medically necessary when policy criteria are met, including postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, androgen deprivation therapy-related bone loss, and aromatase inhibitor-related bone loss.

Specified indications for Wyost (denosumab-bbdz) as medically necessary when policy criteria are met, including prevention of SREs, giant cell tumor of bone, hypercalcemia of malignancy, SRE prevention in castration-resistant prostate cancer, and osteopenia/osteoporosis in systemic mastocytosis.

Marked denosumab-bbdz as unproven and not medically necessary for multiple off-label indications including combination therapy with IV bisphosphonates and several other conditions.

Added HCPCS code Q5136 to the Applicable Codes section.

Updated Background, Clinical Evidence, FDA, and References sections to reflect current information.

12 months

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Coverage Criteria

inv-01: Osteoporosis (postmenopausal/high risk) - Initial Therapy

Jubbonti and Prolia for postmenopausal osteoporosis or to increase bone mass in high‑risk patients — Covered when ALL of the following are met:

Postmenopausal osteoporosis / high fracture risk: Diagnosis of osteoporosis (clinical diagnosis or DXA T‑score per clinical standards); and patient is at high risk for fracture (for example, history of osteoporotic fracture, multiple risk factors for fracture, or failure/intolerance to other available osteoporosis therapy); and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

inv-02: Cancer therapy–associated bone loss and related indications - Initial Therapy

Jubbonti and Prolia for glucocorticoid‑induced osteoporosis, androgen deprivation therapy, and aromatase inhibitor–associated bone loss — Covered when ALL of the following are met:

Glucocorticoid‑induced osteoporosis: Diagnosis of glucocorticoid‑induced osteoporosis; and patient is at high risk for fracture (e.g., history of osteoporotic fracture, multiple risk factors for fracture, or failed/intolerant to other available osteoporosis therapy); and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

Androgen deprivation therapy (non‑metastatic prostate cancer): Diagnosis of non‑metastatic prostate cancer; and patient is receiving androgen deprivation therapy; and one of the following: (1) both history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy (e.g., pamidronate, zoledronic acid); or (2) history of failure or contraindication to oral bisphosphonate therapy; or (3) history of failure, contraindication, or intolerance to IV bisphosphonate therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

Adjuvant aromatase inhibitor therapy (breast cancer): Diagnosis of breast cancer; and patient is receiving aromatase inhibitor therapy; and one of the following: (1) both history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy (e.g., pamidronate, zoledronic acid); or (2) history of failure or contraindication to oral bisphosphonate therapy; or (3) history of failure, contraindication, or intolerance to IV bisphosphonate therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

inv-03: Oncology-related bone disease - Initial Therapy

Wyost and Xgeva for oncology‑related bone indications — Covered when ALL of the following are met:

Prevention of skeletal‑related events (multiple myeloma or bone metastases): Patient is ≥ 18 years of age or a skeletally mature adolescent; and diagnosis of multiple myeloma or metastatic solid tumor with bone metastases; and individual has an expected survival of three months or greater; and refractory (within the past 30 days), contraindication (including renal insufficiency), or intolerance to IV bisphosphonate therapy (e.g., pamidronate, zoledronic acid); and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

Giant cell tumor of bone: Patient is ≥ 18 years of age or a skeletally mature adolescent; and diagnosis of localized, recurrent, or metastatic giant cell tumor of the bone; and disease is unresectable or surgical resection is likely to result in severe morbidity; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Initial therapy

Hypercalcemia of malignancy: Patient is ≥ 18 years of age or a skeletally mature adolescent; and diagnosis of hypercalcemia of malignancy (albumin‑corrected serum calcium > 12.5 mg/dL); and no pre‑existing hypocalcemia; and refractory (within the past 30 days), contraindication (including renal insufficiency), or intolerance to IV bisphosphonate therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

inv-04: Reauthorization/Continuation Criteria

Reauthorization / Continuation of Care — Covered when ALL of the following are met:

General reauthorization: Documentation of positive clinical response to therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Applies to multiple indications

Oncology‑specific reauthorization: For oncology indications, individual has expected survival of three months or greater where required; and documentation of positive clinical response to therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months≥ 3 months expected survival where required

Oncology indications

inv-05: Evidence and mechanism (informational)

Clinical evidence and mechanism summaries included in this excerpt (informational):

Mechanism of action: Denosumab and denosumab‑bbdz bind RANKL, preventing RANK activation on osteoclasts and osteoclast precursors, inhibiting osteoclast formation/function and decreasing bone resorption, thereby increasing bone mass and strength

Informational

Postmenopausal osteoporosis evidence: Phase 3 trials (e.g., FREEDOM and extension) demonstrate reduced fracture incidence and lower exposure‑adjusted fracture rates with denosumab versus placebo; denosumab increased BMD compared with alendronate in randomized trials (60 mg SC Q6M)

Informational

Men and ADT evidence: Randomized studies in men, including those receiving androgen deprivation therapy, showed increases in BMD and reduced vertebral fractures with denosumab

Informational

inv-06: Covered Indications (label-consistent)

Covered when ALL of the following are met for the indicated labeled uses (per product):

Postmenopausal osteoporosis (Prolia/Jubbonti): History of osteoporotic fracture or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy; dosing per FDA labeling

Prolia/Jubbonti labeled indication

Men with osteoporosis or receiving androgen deprivation therapy (Prolia/Jubbonti): Men at high risk for fracture or men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass; dosing per FDA labeling

Prolia labeled indication; demonstrated reduction in vertebral fractures in ADT population

Glucocorticoid‑induced osteoporosis: Adults receiving ≥7.5 mg prednisone daily (or equivalent) and expected to remain on glucocorticoids ≥6 months, at high risk for fracture; dosing per FDA labeling≥ 7.5 mg/day prednisone equivalent; ≥6 months expected use

Denosumab and denosumab-bbdz are considered unproven and not medically necessary when used for combination therapy with intravenous bisphosphonates. The following indications are also considered unproven and not medically necessary: bone loss associated with hormone‑ablation therapy (other than aromatase inhibitors) in breast or prostate cancer, cancer pain, central giant cell granuloma, hyper‑parathyroidism, immobilization hypercalcemia, osteogenesis imperfecta, and osteopenia.

No explicit exclusion criteria beyond the listed unproven/not medically necessary uses are stated in the Applicable Codes section of the policy excerpt.

Denosumab‑bbdz (biosimilars such as Jubbonti and Wyost) are unproven and not medically necessary when used in combination with intravenous bisphosphonates and for the same off‑label indications identified for denosumab in the policy. This policy revision clarifies that the exclusion applies to combination therapy with intravenous bisphosphonates and extends the unproven/not medically necessary determination to denosumab‑bbdz products.

Additional indications specifically listed as unproven/not medically necessary include: bone loss associated with hormone‑ablation therapy (other than aromatase inhibitors), cancer pain, central giant cell granuloma, hyper‑parathyroidism, immobilization hypercalcemia, osteogenesis imperfecta, and osteopenia.

Within the extracted Applicable Codes content there are no explicit statements describing other not medically necessary conditions; the document lists codes and applicable diagnoses without additional 'not medically necessary' entries in that section.

Policy exclusions (denials) for denosumab and denosumab‑bbdz include: combination therapy with intravenous bisphosphonates and the following off‑label uses — bone loss associated with hormone‑ablation therapy (other than aromatase inhibitors), cancer pain, central giant cell granuloma, hyper‑parathyroidism, immobilization hypercalcemia, osteogenesis imperfecta, and osteopenia. These are explicitly listed as unproven and not medically necessary in the revision notes.

Initial Therapy Criteria

inv-46: Initial Therapy Requirements

Initial therapy coverage is indication‑specific and requires meeting ALL of the following general requirements:

Initial therapy general: Meet the indication‑specific diagnostic and risk criteria described in each indication; document prior bisphosphonate failure, contraindication, or intolerance where specified; dosing consistent with FDA labeling; and authorization is for no more than 12 months

See individual indication nodes for detail

inv-48: Initial therapy criteria (selected)

Key labeled initiation criteria and selected trial‑based initiation details (informational):

Trial dosing (informational): Denosumab 60 mg subcutaneous every six months (Q6M) used in pivotal phase 3 trials in postmenopausal women and men with low BMD; dosing and outcomes summarized in FREEDOM, Brown et al., Langdahl et al., Orwoll et al.

Informational

Continuation / Reauthorization Criteria

inv-49: Continuation/Reauthorization

Continuation requires documented positive clinical response and adherence to FDA dosing — Covered when ALL of the following are met:

Continuation general: Documentation of positive clinical response to therapy; and dosing is in accordance with the United States Food and Drug Administration approved labeling; and authorization is for no more than 12 months

Applies to multiple indications including osteoporosis and oncology

inv-04: Reauthorization/Continuation Criteria (duplicate mapping for emphasis)

Reauthorization / Continuation checks (emphasized):

Reauthorization checks: For reauthorization, provide documentation of positive clinical response to therapy; for oncology indications document expected survival where required (e.g., ≥ 3 months); continue dosing per FDA label; authorization limited to no more than 12 months≥ 3 months expected survival where required

Coding

Covered HCPCS CodesHCPCSCovered

J0897	Injection, denosumab, 1 mg
Q5136	Injection, denosumab (Jubbonti/Wyost), biosimilar, 1 mg

Example ICD-10 CodesICD-10

C61	Malignant neoplasm of prostate
C79.81	Secondary malignant neoplasm of breast
E83.52	Hypercalcemia
M81.0	Age-related osteoporosis without current pathological fracture
Z79.52	Long-term (current) use of systemic steroids

Applicable ICD-10 Codes for Jubbonti and ProliaICD-10

M80.039S	Age-related osteoporosis with current pathological fracture, unspecified forearm, sequela
M80.00XA	Age-related osteoporosis with current pathological fracture, unspecified site, initial encounter for fracture
M80.00XD	Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with routine healing
M80.00XG	Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with delayed healing
M80.00XK	Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with nonunion
M80.00XP	Age-related osteoporosis with current pathological fracture, unspecified site, subsequent encounter for fracture with malunion
M80.0B1A	Age-related osteoporosis with current pathological fracture, right pelvis, initial encounter for fracture
M80.0B2A	Age-related osteoporosis with current pathological fracture, left pelvis, initial encounter for fracture
M80.0B9A	Age-related osteoporosis with current pathological fracture, unspecified pelvis, initial encounter for fracture
M80.011A	Age-related osteoporosis with current pathological fracture, right shoulder, initial encounter for fracture

1–10 of 58

1/6

Applicable HCPCS Codes (added)HCPCS

Q5136

Injection, denosumab (Jubbonti/Wyost), biosimilar, 1 mg

Key clinical thresholds and policy date

Expected survival / serum calcium thresholdAlbumin-corrected serum calcium > 12.5 mg/dL required for hypercalcemia of malignancy indication; no pre-existing hypocalcemia

Policy Effective Date2025-04-01

FRAX 10-year risk thresholds (US)Major osteoporotic fracture >= 20% OR hip fracture >= 3%

Glucocorticoid dose threshold>= 7.5 mg prednisone daily (or equivalent) for at least 3 months

Provider Actions & Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required for Jubbonti and Prolia. Initial and reauthorization requests are limited to no more than 12 months and must meet indication-specific criteria in the policy. Jubbonti and Wyost (denosumab-bbdz products) are included in UnitedHealthcare's Review at Launch program; some members may not be eligible for coverage at launch — refer to the Medical Benefit Drug Policy titled Review at Launch for New to Market Medications for details.

Initial and continuation authorizations: limited to ≤ 12 months and must meet indication-specific criteria (see policy criteria for osteoporosis, cancer-related indications, giant cell tumor of bone, hypercalcemia of malignancy, etc.).
Jubbonti and Wyost added to Review at Launch — prior authorization may be required and some members may be ineligible at launch.
Providers must document diagnosis, risk status, prior therapy history (including bisphosphonate failure, intolerance, or contraindication when required), and clinical response for reauthorization.
Claims for Jubbonti and Prolia should include one of the listed ICD-10 diagnosis codes; claims may be denied if submitted without an applicable ICD-10 code.

Site of Care & Administration

Note

No explicit site-of-care restrictions listed

The policy does not state any explicit site-of-care restrictions in this section; providers may administer denosumab in the usual settings per plan and clinical practice.

Check member plan for any site-of-care requirements or restrictions before scheduling infusion/administration.

Note

Dosing and typical administration sites: 120 mg monthly (SRE) vs 60 mg Q6M (osteoporosis)

Denosumab dosing in trials and labeling differs by indication: prevention of skeletal-related events is dosed monthly at 120 mg subcutaneously, while Prolia for osteoporosis is dosed 60 mg subcutaneously every 6 months; administration typically occurs in an office or infusion center depending on plan.

Confirm dosing schedule and site of administration with FDA labeling and the member’s benefit plan prior to treatment.

Reference and Biosimilar Products

Billing Rule

Policy covers Prolia/Xgeva and biosimilars (Jubbonti, Wyost)

Policy includes both reference products (Prolia, Xgeva) and biosimilars; Jubbonti and Wyost have been added to the Review at Launch program as denosumab-bbdz products.

Some members may not be eligible for coverage of Jubbonti or Wyost at this time per the Review at Launch policy.

Billing Rule

Jubbonti and Wyost added to product list with specified covered indications

Jubbonti and Wyost have been added to the product list and are included in the Review at Launch program; they are listed with specified covered indications when the policy criteria are met.

Policy revision notes specify that Jubbonti is proven/medically necessary for listed osteoporosis indications when criteria are met and Wyost for listed oncology indications.

Step Therapy

Requirement	Details
Document prior bisphosphonate failure, contraindication, or intolerance
For certain indications (e.g., androgen deprivation therapy for non‑metastatic prostate cancer; prevention of skeletal‑related events in patients with bone metastases or multiple myeloma), approval requires documentation of prior failure, contraindication, or intolerance to oral and/or IV bisphosphonate therapy. Policy language specifies history of failure or contraindication to oral bisphosphonates, and/or history of failure, contraindication, or intolerance to IV bisphosphonates (e.g., pamidronate, zoledronic acid).

Requirement

Details

Document prior bisphosphonate failure, contraindication, or intolerance

For certain indications (e.g., androgen deprivation therapy for non‑metastatic prostate cancer; prevention of skeletal‑related events in patients with bone metastases or multiple myeloma), approval requires documentation of prior failure, contraindication, or intolerance to oral and/or IV bisphosphonate therapy. Policy language specifies history of failure or contraindication to oral bisphosphonates, and/or history of failure, contraindication, or intolerance to IV bisphosphonates (e.g., pamidronate, zoledronic acid).

Evidence / Note	Implication for Step Therapy
Phase 3 trial (Brown et al.) compared denosumab 60 mg subcutaneously every 6 months with oral alendronate 70 mg weekly in postmenopausal women; denosumab produced significantly greater increases in BMD at 12 months and greater reductions in bone turnover markers.
Informational: comparative efficacy versus alendronate is described in clinical trials but the trial summary does not impose an explicit additional step requirement beyond the policy's bisphosphonate failure/intolerance criteria.

Requirement	Policy Detail
Failure or intolerance to other osteoporosis therapy may be required
Policy indicates that, for some labeled indications (for example postmenopausal osteoporosis, glucocorticoid‑induced osteoporosis, androgen deprivation therapy, and adjuvant aromatase inhibitor therapy), approval may require failure or intolerance to other available osteoporosis therapies per the labeled indication and the criteria in the policy. Specific examples include prior failure or contraindication to oral bisphosphonates and/or refractory/contraindication/intolerance to IV bisphosphonates.

Requirement

Policy Detail

Failure or intolerance to other osteoporosis therapy may be required

Policy indicates that, for some labeled indications (for example postmenopausal osteoporosis, glucocorticoid‑induced osteoporosis, androgen deprivation therapy, and adjuvant aromatase inhibitor therapy), approval may require failure or intolerance to other available osteoporosis therapies per the labeled indication and the criteria in the policy. Specific examples include prior failure or contraindication to oral bisphosphonates and/or refractory/contraindication/intolerance to IV bisphosphonates.

Definitions

inv-40: Skeletally mature adolescent

DefinitionSkeletally mature adolescent: defined as having at least one mature long bone (e.g., closed epiphyseal growth plate of the humerus)

Age equivalenceSkeletally mature adolescents are considered equivalent to adults for selected denosumab oncology and giant cell tumor indications when maturity criterion met

Use in criteriaPolicy requires patient be ≥18 years OR a skeletally mature adolescent (per definition) for Wyost/Xgeva oncology indications

inv-41: Hypercalcemia of malignancy

DefinitionHypercalcemia of malignancy defined as albumin‑corrected serum calcium level greater than 12.5 mg/dL

Pre‑existing hypocalcemia exclusion

Background & Clinical Evidence

Denosumab and its biosimilars are monoclonal antibody RANK ligand inhibitors that reduce osteoclast activity and bone resorption. FDA‑labeled uses include treatment of osteoporosis to increase bone mass and reduce fracture risk, prevention of skeletal‑related events in patients with bone metastases or multiple myeloma, treatment of giant cell tumor of bone, and treatment of hypercalcemia of malignancy. The policy distinguishes labeled, medically necessary uses from listed unproven/off‑label indications and applies indication‑specific coverage criteria and authorization requirements.

inv-05: Evidence and mechanism (placed also under Background for narrative)

Evidence and mechanism summaries (also placed under Background for narrative) — informational only:

Mechanism of action: Denosumab and denosumab‑bbdz bind RANKL, preventing osteoclast activation and reducing bone resorption; RANKL/RANK signaling is implicated in bone metastases and giant cell tumor pathophysiology

Informational

Clinical outcomes summary: Pivotal trials demonstrated increased BMD and fracture risk reduction in osteoporosis populations and BMD benefit in men on ADT; denosumab showed non‑inferiority/superiority to risedronate in glucocorticoid‑induced osteoporosis studies

Revision History

2025-04-01policy_revisionLatest

Title changed from 'Denosumab (Prolia ® & Xgeva ® ) Coverage Rationale' and Jubbonti (denosumab-bbdz) and Wyost (denosumab-bbdz) were added to the list of applicable products; language added that these biosimilars are included in the Review at Launch program and some members may not be eligible for coverage at this time.

2025-04-01coverage_update

Specified indications for Jubbonti as medically necessary when policy criteria are met, including postmenopausal osteoporosis and to increase bone mass in patients at high risk for fracture.

2025-04-01coverage_update

Policy Summary

PayerUnitedHealthcare

PolicyDenosumab (brand and biosimilar) coverage

Policy CodePolicy IEXD0068.11

Change TypeProduct list updateReview at Launch addedindication clarifications

Effective DateApr 1, 2025

Next Review DateN/A

Key ActionObtain prior authorization (initial approvals limited to 12 months) and document diagnosis, risk status, and prior bisphosphonate failure or intolerance when required.

SourceLink

On This Page

Billing Rule

Applicable Diagnosis Codes Required

Use the policy's enumerated ICD-10 codes when requesting authorization and when submitting claims for Jubbonti and Prolia. The policy lists extensive ICD-10 codes for osteoporosis with and without current pathological fracture, malignant neoplasm of prostate, secondary malignant neoplasm of breast, and other applicable diagnoses. Failure to use one of the listed diagnosis codes may result in claim denial.

Examples of included ICD-10 codes: C61 (Malignant neoplasm of prostate); C79.81 (Secondary malignant neoplasm of breast); multiple M80.* codes for osteoporosis with current pathological fracture (see policy for full list).
Providers must select the most specific ICD-10 code that matches the member's diagnosis as listed in the policy when submitting claims and prior authorization requests.

Step Therapy

Step Therapy / Prior Treatment Requirements

Step therapy requirements apply for certain indications: before denosumab products are approved for some indications, documentation of prior bisphosphonate therapy failure, contraindication, or intolerance is required per the indication-specific criteria.

For androgen deprivation or aromatase inhibitor–associated bone loss, documentation must show history of intolerance to oral bisphosphonates and history of failure/contraindication/intolerance to IV bisphosphonates, or alternative listed failures/contraindications per the policy.
For cancer-related skeletal indications (Wyost/Xgeva), refractory, contraindication (including renal insufficiency), or intolerance to IV bisphosphonate therapy must be documented.

Documentation Required

Documentation Required for Authorization

Required documentation for initial and continuation requests must be submitted with the prior authorization: include the member's diagnosis (using a listed ICD-10 code), high-risk fracture status or indication-specific risk factors, prior therapy history (including bisphosphonate failure/intolerance/contraindication when applicable), current concomitant therapies (e.g., androgen deprivation or aromatase inhibitor therapy), dosing consistent with FDA labeling, and evidence of clinical response for reauthorization.

Initial requests: diagnosis (ICD-10), risk status, prior therapies and rationale for denosumab use, planned dosing per FDA labeling.
Continuation/reauthorization requests: documentation of positive clinical response, confirmation of ongoing indication (e.g., continued androgen deprivation or aromatase inhibitor therapy when applicable), and dosing consistent with FDA labeling.
Authorization duration: requests (initial and reauthorization) are approved for no more than 12 months at a time.