Colorado Rocky Mountain Health Plans denosumab Coverage update

Coverage Criteria

Initial and continuation therapy — postmenopausal osteoporosis

Bildyos, Conexxence, Jubbonti, Prolia, and Stoboclo are proven and medically necessary for postmenopausal osteoporosis or to increase bone mass in patients at high risk for fracture when ALL of the following are met:

Initial Therapy for postmenopausal osteoporosis: Diagnosis of osteoporosis; AND one of: (1) BMD T-score ≤ -2.5 at lumbar spine (≥2 vertebrae), hip (femoral neck/total hip), or one-third radius; OR (2) history of a minimal-trauma fracture at one of the following sites: vertebral compression, hip, distal radius, pelvis, or proximal humerus; OR both: BMD T-score between -1 and -2.5 and FRAX 10-year probability meeting thresholds (major osteoporotic fracture ≥ 20% OR hip fracture ≥ 3%); AND one of the following prior therapy criteria: (A) history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy (e.g., pamidronate, zoledronic acid); OR (B) history of failure or contraindication to oral bisphosphonate therapy; OR (C) 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.see thresholds

Reauthorization requires provider attestation of positive clinical response and adherence to FDA dosing.

ADT-associated bone loss

For patients receiving androgen deprivation therapy for non-metastatic prostate cancer:

Indication: increase bone mass on ADT: Diagnosis of non-metastatic prostate cancer; AND patient is receiving androgen deprivation therapy; AND one of the prior therapy criteria: (A) history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy; OR (B) history of failure or contraindication to oral bisphosphonate therapy; OR (C) 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.

Reauthorization requires continued ADT, provider attestation of positive clinical response, and FDA dosing.

Aromatase inhibitor-associated bone loss

For patients receiving adjuvant aromatase inhibitor therapy for breast cancer:

Indication: increase bone mass on aromatase inhibitor: Diagnosis of breast cancer; AND patient is receiving aromatase inhibitor therapy; AND one of the prior therapy criteria: (A) history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy; OR (B) history of failure or contraindication to oral bisphosphonate therapy; OR (C) 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.

Reauthorization requires continued aromatase inhibitor therapy and provider attestation of positive clinical response.

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis in patients at high risk for fracture:

Glucocorticoid-induced osteoporosis: Diagnosis of glucocorticoid-induced osteoporosis; AND history of prednisone or equivalent ≥ 5 mg/day for ≥ 3 months; AND one of: BMD T-score ≤ -2.5 at lumbar spine (≥2 vertebrae), hip (femoral neck/total hip), or one-third radius; OR history of a minimal-trauma fracture (vertebral compression, hip, distal radius, pelvis, proximal humerus); OR FRAX 10-year probability meeting thresholds (major osteoporotic fracture ≥ 20% OR hip fracture ≥ 3%); AND one of the prior therapy criteria: (A) history of intolerance to oral bisphosphonate therapy AND history of failure, contraindication, or intolerance to IV bisphosphonate therapy; OR (B) history of failure or contraindication to oral bisphosphonate therapy; OR (C) 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.see thresholds

Reauthorization: provider attests to positive clinical response and FDA dosing.

Oncologic indications and related continuation criteria

Bilprevda, Bomyntra, Osenvelt, Wyost, and Xgeva are proven and medically necessary for oncologic skeletal indications 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 presence of metastatic disease secondary to a solid tumor with bone metastases; AND individual has an expected survival of ≥ 3 months; 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.

Reauthorization: expected survival ≥ 3 months and provider attestation of positive clinical response.

Giant cell tumor of bone: Patient is ≥ 18 years of age or a skeletally mature adolescent; AND diagnosis of localized or metastatic giant cell tumor of 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.

Reauthorization: provider attestation of positive clinical response.

Mastocytosis-related bone disease

Osteopenia/osteoporosis in systemic mastocytosis with bone pain not responding to bisphosphonates:

Systemic mastocytosis with bone pain: Diagnosis of systemic mastocytosis; AND patient has bone pain; AND diagnosis of osteoporosis or osteopenia defined as BMD T-score ≤ -1 at lumbar spine (≥2 vertebrae), hip (femoral neck, total hip), or one-third radius OR history of a minimal-trauma fracture (vertebral compression, hip, distal radius, pelvis, proximal humerus); 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.BMD T-score ≤ -1

Reauthorization: provider attestation of positive clinical response.

Initial Therapy

Covered when ALL of the following are met

Initial Therapy Criteria: Diagnosis of systemic mastocytosis; AND patient has bone pain; AND diagnosis of osteoporosis or osteopenia based on either BMD T-score ≤ -1 at lumbar spine (≥2 vertebral bodies), hip (femoral neck, total hip), or radius (one-third radius) OR history of a minimal-trauma fracture (vertebral compression, hip, distal radius, pelvis, proximal humerus); 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 for no more than 12 months.12 months

Reauthorization/Continuation of Care

Covered for continuation when ALL of the following are met

Reauthorization Criteria: Provider attests to a positive clinical response; AND dosing is in accordance with the United States Food and Drug Administration approved labeling; AND authorization is for no more than 12 months.12 months

Evidence summary for covered indications

Clinical trial evidence and outcomes cited supporting use of denosumab in specified populations

Postmenopausal osteoporosis evidence: Denosumab 60 mg every 6 months increased BMD versus alendronate and reduced bone turnover markers with similar safety (Brown et al.); FREEDOM extension analysis showed lower exposure-adjusted fracture incidence for denosumab versus placebo over combined follow-up up to 10 years (Kendler et al.).

References: Brown JP trial; FREEDOM extension analysis.

Evidence summary — men

Men with low BMD

Men with low BMD: Denosumab demonstrated significant increases in BMD at multiple skeletal sites and was well tolerated in phase 3 trials in men; benefits continued with second-year treatment (Langdahl et al.; Orwoll et al.).

Evidence summary — ADT patients

Patients receiving androgen-deprivation therapy for nonmetastatic prostate cancer

ADT-associated bone loss: Denosumab 60 mg subcutaneously every 6 months increased lumbar spine BMD (5.6% at 24 months) and decreased new vertebral fractures at 36 months (1.5% vs 3.9%; relative risk 0.38) in a randomized trial (Smith et al., NCT00089674).

Postmenopausal Osteoporosis

FDA-labeled indications and contexts referenced in the document

Osteoporosis (postmenopausal women): Treatment of postmenopausal women with osteoporosis at high risk for fracture, or who failed/intolerant to other therapy; reduces vertebral, nonvertebral, and hip fractures.

(FDA indication; Prolia and biosimilars)

Men with Osteoporosis

Men with osteoporosis: Treatment to increase bone mass in men with osteoporosis at high risk for fracture or who failed/intolerant to other therapy.

(FDA indication)

ADT-associated Bone Loss

Men receiving ADT for nonmetastatic prostate cancer: Increase bone mass and reduce incidence of vertebral fractures; denosumab 60 mg subcutaneously every 6 months demonstrated BMD increases and reduced new vertebral fractures at 36 months.

(FDA indication and trial data NCT00089674)

Glucocorticoid-Induced Osteoporosis

Glucocorticoid-induced osteoporosis: Treatment in men and women at high risk of fracture who are initiating or continuing systemic glucocorticoids ≥ 7.5 mg prednisone equivalent and expected to remain on glucocorticoids ≥ 6 months; denosumab was non-inferior and superior to risedronate for lumbar spine BMD at 12 months in a randomized trial.>=7.5 mg prednisone daily

(Study NCT01575873)

Oncology — SRE Prevention

Prevention of skeletal-related events (SRE) in malignancy: Denosumab 120 mg every 4 weeks is indicated for prevention of SREs in patients with bone metastases from solid tumors and multiple myeloma; trials show noninferiority to zoledronic acid and, in some analyses (e.g., castration-resistant prostate cancer), delayed time to first SRE (HR 0.82).

(FDA indications; phase 3 trials and NCCN guidance)

Giant Cell Tumor of Bone

Giant cell tumor of bone: Denosumab is indicated for unresectable disease or where resection would cause severe morbidity; recommended by NCCN as single agent or in combination approaches for resectable disease with unacceptable morbidity and as preferred therapy for unresectable metastatic disease or prior to surgery for resectable recurrence.

(FDA indication and NCCN recommendations)

This policy is the UnitedHealthcare Medical Benefit Drug Policy framework applied for Colorado Rocky Mountain Health Plans members. It does not replace or override federal, state, or specific contractual benefit plan terms; when there is a conflict, the applicable federal, state, or contractual requirements govern coverage determinations. Refer to state-specific guidance where noted for exclusions of policy application.

Combination use of denosumab (and its biosimilars) together with intravenous bisphosphonates is considered unproven and not medically necessary and is explicitly listed among indications that are not supported by the policy.

Within the cited applicable-code sections there are no additional explicit policy exclusions beyond those listed elsewhere; code lists are provided for documentation and authorization support rather than to define exclusions.

Clinical trial data note an increased incidence of hypocalcemia with denosumab compared with zoledronic acid. This safety profile observation may influence clinical decisions and coverage consideration for patients at risk for hypocalcemia and should be considered when assessing medical necessity.

The policy identifies a set of conditions for which denosumab and listed biosimilars are considered unproven and not medically necessary, including: combination therapy with IV bisphosphonates; bone loss associated with hormone-ablation therapy other than aromatase inhibitors in breast cancer; cancer pain; central giant cell granuloma; hyperparathyroidism; immobilization hypercalcemia; osteogenesis imperfecta; and osteopenia.

In the applicable-code excerpts reviewed there are no standalone 'not medically necessary' statements; the explicit not medically necessary determinations appear in the policy’s Unproven and Not Medically Necessary section rather than the code listings.

This Medical Benefit Drug Policy is informational and intended to assist interpretation of standard UnitedHealthcare benefit plans. Coverage is ultimately governed by the terms of the applicable federal, state, or contractual benefit plan; providers should verify those requirements when making coverage or authorization requests.

Coding

Applicable HCPCS/CodesHCPCS

J0897	Injection, denosumab, 1 mg. Brand Name = Prolia and Xgeva.
Q5136	Injection, denosumab (jubbonti/wyost), biosimilar, 1 mg. Brand Name = Jubbonti and Wyost.
Q5157	Injection, denosumab-bmwo (Stoboclo/Osenvelt), biosimilar, 1 mg. Brand Name = Stoboclo and Osenvelt.
Q5158	Injection, denosumab-bnht (Bomyntra/Conexxence), biosimilar, 1 mg. Brand Name = Bomyntra and Conexxence.
Q5162	Injection, denosumab-nxxp (bildyos/bilprevda), biosimilar, 1 mg. Brand Name = Bildyos and Bilprevda.

Applicable ICD-10 Codes (selected examples from long list)ICD-10

C61	Malignant neoplasm of prostate.
C79.81	Secondary malignant neoplasm of breast.
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.
M80.0AXA	Age-related osteoporosis with current pathological fracture, other site, initial encounter for fracture.
M80.0B1A	Age-related osteoporosis with current pathological fracture, right pelvis, initial encounter for fracture.
M80.011A	Age-related osteoporosis with current pathological fracture, right shoulder, initial encounter for fracture.
M80.012A	Age-related osteoporosis with current pathological fracture, left shoulder, initial encounter for fracture.
M80.021A	Age-related osteoporosis with current pathological fracture, right humerus, initial encounter for fracture.
M80.031A	Age-related osteoporosis with current pathological fracture, right forearm, initial encounter for fracture.

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Applicable ICD-10 Codes (selected examples)ICD-10

M80.811A	Other osteoporosis with current pathological fracture, right shoulder, initial encounter for fracture
M80.811D	Other osteoporosis with current pathological fracture, right shoulder, subsequent encounter for fracture with routine healing
M80.811G	Other osteoporosis with current pathological fracture, right shoulder, subsequent encounter for fracture with delayed healing
M80.811K	Other osteoporosis with current pathological fracture, right shoulder, subsequent encounter for fracture with nonunion
M80.811P	Other osteoporosis with current pathological fracture, right shoulder, subsequent encounter for fracture with malunion
M80.811S	Other osteoporosis with current pathological fracture, right shoulder, sequela
M80.8AXA	Other osteoporosis with current pathological fracture, other site, initial encounter for fracture
M80.8AXD	Other osteoporosis with current pathological fracture, other site, subsequent encounter for fracture with routine healing
M80.8AXG	Other osteoporosis with current pathological fracture, other site, subsequent encounter for fracture with delayed healing
M80.8AXK	Other osteoporosis with current pathological fracture, other site, subsequent encounter for fracture with nonunion

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Applicable HCPCS Codes (updated)HCPCS

Q5162

Updated HCPCS code replacing C9399, J3490, J3590, J9999 as listed

inv-29: BMD T-score (osteoporosis)

BMD T-score threshold for osteoporosis≤ -2.5 at lumbar spine (≥2 vertebral bodies), femoral neck/total hip, or one‑third radius

Alternate diagnostic criteriaT-score between -1 and -2.5 plus FRAX meeting clinical thresholds (see FRAX block)

Site requirementsLumbar spine measured at ≥2 vertebral bodies, hip (femoral neck/total hip), or one‑third radius

inv-30: FRAX 10-year fracture probability

FRAX 10‑year thresholds used for eligibilityMajor osteoporotic fracture ≥ 20% OR hip fracture ≥ 3%

Use with BMD

Provider Actions and Authorization Requirements

Prior Authorization

Prior authorization and authorization period

Prior authorization required. Authorization period: initial approvals limited to no more than 12 months for covered indications; reauthorization/continuation criteria require provider attestation of positive clinical response and expected survival >= 3 months when applicable.

Authorization period: up to 12 months for initial therapy and reauthorization where specified
Provider attestation required for continuation/reauthorization (positive clinical response)
Expected survival >= 3 months required for oncology-related indications (e.g., bone metastases, multiple myeloma)

Documentation Required

Initial Therapy Authorization — required clinical documentation

Initial therapy requests must document the specific diagnosis (see relevant diagnosis codes below), clinical findings supporting the indication (e.g., BMD T-score, history of fragility fracture, FRAX score where applicable), prior therapies and their adequacy (dose/duration), intolerance or contraindications to preferred products or IV bisphosphonates when required, and dosing consistent with FDA labeling.

Initial Therapy Criteria and Preferred Product Step

Preferred Product Criteria / Step therapy

Preferred product criteria for using non-preferred denosumab products

Criteria for non-preferred product use: Either (A) history of a trial of adequate dose and duration to both preferred products (pairing depends on non-preferred product requested) resulting in minimal clinical response and residual disease activity, AND physician attests that the non-preferred product would be expected to provide superior clinical response; OR (B) history of contraindication, intolerance, or adverse event to both preferred products with physician attestation that the same contraindication/intolerance/adverse event would not be expected with the non-preferred product; AND patient has not had loss of favorable response after established maintenance therapy with the preferred products where applicable.

Applies differently depending on which non-preferred product requested (see policy).

Initial Therapy — top-level node

Initial Therapy (drug-specific): Use for systemic mastocytosis with bone pain and osteoporosis/osteopenia (BMD T-score ≤ -1 or qualifying minimal-trauma fracture) after refractory/contraindication/intolerance to IV bisphosphonates within past 30 days (including renal insufficiency); dosing per FDA labeling; authorization up to 12 months.

Reauthorization and Continuation Criteria

Reauthorization/Continuation of Care

Reauthorization requirements common across indications

Reauthorization standard: Provider attests to a positive clinical response; AND dosing is in accordance with the United States Food and Drug Administration approved labeling; AND authorization is for no more than 12 months (may be repeated with continued attestation and ongoing indication-specific criteria such as continued ADT, aromatase inhibitor therapy, or expected survival where applicable).12 months

Provider must document response and continued indication for therapy.

Reauthorization/Continuation top-level node

Continuation: Provider attests to a positive clinical response AND dosing per FDA labeling AND authorization up to 12 months.12 months

Step Therapy Requirements

Requirement	Details
Trial of preferred denosumab product(s)
Patient must have a trial of the specified preferred products (pairing depends on non-preferred product requested) of adequate dose and duration: either Bildyos + Jubbonti (for requests involving Conexxence, Prolia, or Stoboclo) or Bilprevda + Wyost (for requests involving Bomyntra, Osenvelt, or Xgeva). If prior trial produced only minimal clinical response, physician must attest the non-preferred product would be expected to provide superior response; alternatively, documented contraindication/intolerance to both preferred products with physician attestation that the same adverse event would not be expected with the non-preferred product is acceptable.

Requirement

Details

Trial of preferred denosumab product(s)

Patient must have a trial of the specified preferred products (pairing depends on non-preferred product requested) of adequate dose and duration: either Bildyos + Jubbonti (for requests involving Conexxence, Prolia, or Stoboclo) or Bilprevda + Wyost (for requests involving Bomyntra, Osenvelt, or Xgeva). If prior trial produced only minimal clinical response, physician must attest the non-preferred product would be expected to provide superior response; alternatively, documented contraindication/intolerance to both preferred products with physician attestation that the same adverse event would not be expected with the non-preferred product is acceptable.

Requirement	Details
Trial of IV bisphosphonate therapy
Required unless contraindicated or intolerant. Documentation must show refractory (within past 30 days), contraindication (including renal insufficiency), or intolerance to intravenous bisphosphonate therapy (e.g., pamidronate, zoledronic acid).

Context	Policy note
Comparison trial: denosumab versus alendronate
Clinical trial evidence (Brown et al.) compared denosumab 60 mg Q6M with oral alendronate 70 mg weekly in postmenopausal women and demonstrated greater BMD gains and larger reductions in bone turnover markers with denosumab; the policy cites these data as context for therapy choices but does not establish an alternate step requirement vs alendronate.

Consideration	Details
Prior failure or intolerance to other osteoporosis therapies
FDA-labeled indications and policy language note that patients who have failed or are intolerant to other available osteoporosis therapies (per product labeling) may be appropriate candidates for denosumab; providers should document prior treatment history consistent with labeled indications.

Quantity Limits

inv-72: Denosumab (all formulations) quantity limit summary

Quantity limits summaryNo explicit per‑formulation quantity limit is specified in the policy text for denosumab products (all formulations)

Dosing regimens referencedOsteoporosis: 60 mg subcutaneously every 6 months; Oncology (SRE prevention): 120 mg subcutaneously every 4 weeks—policy cites these regimens

Authorization period related to quantityAuthorizations are limited to no more than 12 months per authorization across indications

Site of Care and Administration

Billing Rule

Office administration (subcutaneous injection); no site restrictions stated

Administration is by subcutaneous injection per the policy; the policy does not impose site‑of‑care restrictions in the cited sections.

Documentation Required

Specify administration setting and dosing: q4 weeks (oncology) vs q6 months (osteoporosis)

For oncology dosing (prevention of skeletal‑related events) denosumab is administered subcutaneously every 4 weeks in trials; for osteoporosis (Prolia) the regimen referenced is 60 mg subcutaneously every 6 months — specify the appropriate regimen on the authorization request.

Oncology/SRE prevention: denosumab 120 mg q4 weeks (trial dosing).
Osteoporosis: denosumab 60 mg q6 months (Prolia dosing).

Biosimilars and Formulary Preference

Billing Rule

Preferred denosumab products require meeting diagnosis criteria

Preferred denosumab products are Bildyos, Bilprevda, Jubbonti, and Wyost; coverage for these products is contingent on meeting the policy’s diagnosis‑specific criteria.

Prior Authorization

Non‑preferred product coverage requires Preferred Product Criteria plus diagnosis criteria

Coverage for non‑preferred denosumab products (Bomyntra, Conexxence, Osenvelt, Prolia, Stoboclo, Xgeva) requires meeting the Preferred Product Criteria in addition to the diagnosis‑specific criteria (trial of preferred products or documented contraindication/intolerance and physician attestation).

Billing Rule

Code mapping: Q5136 ↔ J0897 (Jubbonti/Wyost to Prolia/Xgeva)

The policy maps biosimilar HCPCS Q5136 to the J0897 (Prolia/Xgeva) reference as an equivalent reporting code for certain biosimilars (Q5136 corresponding to J0897 in the code table).

Background

Denosumab is a monoclonal antibody that binds RANKL to inhibit osteoclast formation and bone resorption. It is used clinically as an antiresorptive agent for osteoporosis (including postmenopausal and in men), to prevent skeletal-related events in patients with bone metastases or multiple myeloma, to treat giant cell tumor of bone in selected patients, and for hypercalcemia of malignancy when bisphosphonates are ineffective or contraindicated. These therapeutic roles are supported by FDA-labeled indications and pivotal trials described in the policy.

Definitions

inv-54: Hypercalcemia of malignancy definition

Hypercalcemia of malignancy (policy definition)Albumin‑corrected serum calcium level greater than 12.5 mg/dL (3.1 mmol/L)

Age requirementPatient ≥ 18 years or skeletally mature adolescent (see skeletally mature adolescent definition)

Prior therapy requirementRefractory to, contraindication to, or intolerance of IV bisphosphonate therapy within prior 30 days for this indication

inv-55: Skeletally mature adolescent definition

DefinitionSkeletally mature adolescent defined as having at least 1 mature long bone (e.g., closed epiphyseal growth plate of the humerus)

Age boundary in indicationsPolicy applies to adults (≥18 years) or skeletally mature adolescents for oncology and hypercalcemia indications

OpenPayer

Denosumab and Biosimilars: Medical Benefit Drug Policy — Coverage Criteria

Coverage Criteria

Coding

Provider Actions and Authorization Requirements

Initial Therapy Criteria and Preferred Product Step

Reauthorization and Continuation Criteria

Step Therapy Requirements

Quantity Limits

Site of Care and Administration

Biosimilars and Formulary Preference

Background

Definitions