ModifiedPremera BluecrossPolicy 5.01.658

Denosumab Products

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Defines medical necessity, coverage criteria, dosing limits, and benefit application for branded and biosimilar denosumab products for members of Premera Bluecross.

Policy Summary

PayerPremera Bluecross

PolicyDenosumab Products

Policy CodePolicy 5.01.658

Change TypeUpdated coverage criteria, product preference designations, dose limits, and coding additions

Effective DateAug 7, 2026

Last ReviewJul 1, 2026

Next Review DateAug 7, 2026

Key ActionSubmit medical records including office visit notes with diagnosis and medication history to document medical necessity.

SourceLink

POLICY UPDATE CHANGES

Changed preferred and non-preferred designations for multiple denosumab biosimilars and reference products and updated step requirements between specific products.

Added or clarified a dosing limit of 120 mg every 4 weeks for prevention of skeletal-related events in individuals with multiple myeloma and bone metastases from solid tumors for several denosumab products.

Updated coverage criteria for multiple denosumab products (Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, Xtrenbo).

New HCPCS codes Q5161, Q5162, Q5165, Q5166, Q5167, Q5171 were added to the coding section.

Moved Xgeva (denosumab) from policy 5.01.540 into 5.01.658 and designated preferred/non-preferred status changes for several products (e.g., Xtrenbo to preferred).

60 mgdose limit (osteoporosis)

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ModifiedPremera BluecrossPolicy 5.01.658

Denosumab Products

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Defines medical necessity, coverage criteria, dosing limits, and benefit application for branded and biosimilar denosumab products for members of Premera Bluecross.

Policy Summary

PayerPremera Bluecross

PolicyDenosumab Products

Policy CodePolicy 5.01.658

Change TypeUpdated coverage criteria, product preference designations, dose limits, and coding additions

Effective DateAug 7, 2026

Last ReviewJul 1, 2026

Next Review DateAug 7, 2026

Key ActionSubmit medical records including office visit notes with diagnosis and medication history to document medical necessity.

SourceLink

POLICY UPDATE CHANGES

Changed preferred and non-preferred designations for multiple denosumab biosimilars and reference products and updated step requirements between specific products.

Updated coverage criteria for multiple denosumab products (Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, Xtrenbo).

New HCPCS codes Q5161, Q5162, Q5165, Q5166, Q5167, Q5171 were added to the coding section.

Moved Xgeva (denosumab) from policy 5.01.540 into 5.01.658 and designated preferred/non-preferred status changes for several products (e.g., Xtrenbo to preferred).

60 mgdose limit (osteoporosis)

120 mgdose limit (oncology)

2required bisphosphonates to fail

6 monthsmax initial approval (oncology)

Coverage Criteria and Medical Necessity

inv-01: Denosumab coverage criteria by indication and product

Coverage and medical necessity criteria vary by specific denosumab product and indication (osteoporosis, increase bone mass with ADT or aromatase inhibitor therapy, prevention/treatment of skeletal-related events, hypercalcemia of malignancy, giant cell tumor of bone).

ALL of the following

Indication: osteoporosis OR to increase bone mass in men receiving androgen deprivation therapy for nonmetastatic prostate cancer OR to increase bone mass in women receiving adjuvant aromatase inhibitor therapy for breast cancer
Medication trial requirement: tried and had inadequate response or intolerance to 2 generic bisphosphonates (either 2 oral agents OR 1 oral agent and 1 IV agent) unless bisphosphonates are contraindicated
Dose/interval threshold: dose limited to 60 mg every 6 months

ALL of the following

Indication: osteoporosis OR to increase bone mass with ADT or aromatase inhibitor therapy (as above)
Step requirement: individual has tried and had an inadequate response or intolerance to Bildyos (denosumab-nxxp) AND Enoby (denosumab-qbde)
Dose/interval threshold: dose limited to 60 mg every 6 months

ALL of the following

Indication: men on ADT for nonmetastatic prostate cancer OR women on adjuvant aromatase inhibitor therapy for breast cancer
Dose/interval threshold (applicable products): 60 mg every 6 months

ALL of the following

Indication: prevention of SREs for individuals with multiple myeloma OR individuals with bone metastases from solid tumors
For breast cancer patients: expected survival ≥ 3 months

ALL of the following

Indication: prevention of SREs in multiple myeloma OR bone metastases from solid tumors; treatment of prostate cancer with castration‑recurrent disease (when specified)
Prior therapy requirement: documented inadequate response or intolerance to IV zoledronic acid 4 mg
Additional step: individual has tried and had an inadequate response or intolerance to Bilprevda (denosumab-nxxp) AND Xtrenbo (denosumab-qbde) when required by product-specific criteria
Dose/interval threshold: dose limited to 120 mg every 4 weeks

ALL of the following

Bilprevda and Xtrenbo: may be considered medically necessary for treatment
Other products: considered medically necessary only after documented inadequate response or intolerance to Bilprevda AND Xtrenbo

ALL of the following

All uses not specifically outlined in this policy are considered investigational

ALL of the following

Certain denosumab products administered subcutaneously every 6 months are managed through medical and pharmacy benefits
Oral bisphosphonates are considered contraindicated in individuals with esophageal disorders (e.g., achalasia, esophageal stricture, Barrett's esophagus, esophageal varices); if oral bisphosphonates are contraindicated, only IV zoledronic acid is required before denosumab

ALL of the following

Initial and renewal approval durations vary by product group: some oncology products initial reviews up to 6 months, may extend to 12 months; certain stable products may be approved up to 2 years

inv-02: Coverage criteria and product preference

Preferred status and step requirements per 2026 updates

ALL of the following

Preferred denosumab products: Bildyos (denosumab-nxxp) and Enoby (denosumab-qbde)

ALL of the following

Non‑preferred denosumab products require documented inadequate response or intolerance to specified preferred products prior to approval

Non‑preferred requiring prior trial of Bildyos AND Enoby

Boncresa (denosumab-mobz)
Bosaya (denosumab-kyqq)

inv-03: Prevention of skeletal-related events

Updated coverage criteria and dosing limits for denosumab products.

ALL of the following

Dose is limited to 120 mg every 4 weeks for prevention of skeletal‑related events in individuals with multiple myeloma and in individuals with bone metastases from solid tumors
Products to which this dose limit applies include: Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo

inv-04: Administrative and coding notes

Policy history indicates product preference changes and movement of Xgeva into this policy; coding additions affect billing.

ALL of the following

Xgeva (denosumab) was moved from policy 5.01.540 (Miscellaneous Oncology Drugs) into policy 5.01.658
Coverage criteria and product listings for multiple denosumab products were added across 2025–2026 interim reviews (see history entries) and preference statuses were changed in the 2026 update

ALL of the following

New HCPCS codes were added affecting denosumab billing: Q5161 and Q5162 (effective 04/01/26) and Q5165, Q5166, Q5167, Q5171 (effective 07/01/26)
J3590 and J0897 and other existing codes remain referenced in the coding section (see Coding block) and some products were added as parenthetical examples to J3590

ALL of the following

Billing and Coding

HCPCS/CPT denosumab codesHCPCS

J0897	Injection, denosumab (Prolia/Xgeva) 1 mg
J3590	Unclassified biologics (use to report: Aukelso, Bildyos, Bilprevda, Boncresa, Bosaya, Enoby, Jubereq, Osvyrti, Oziltus, and Xtrenbo)
J9999	Not otherwise classified (use to report: Bilprevda)
Q5136	Injection, denosumab-bbdz (Jubbonti/Wyost), biosimilar, 1 mg
Q5157	Injection, denosumab-bmwo (Stoboclo/Osenvelt), biosimilar, 1 mg (new code effective 10/01/25)
Q5158	Injection, denosumab-bnht (Bomyntra/Conexxence), biosimilar, 1 mg (new code effective 10/01/25)
Q5159	Injection, denosumab-dssb (Ospomyv/Xbryk), biosimilar, 1 mg (new code effective 10/01/25)
Q5161	Injection, denosumab-kyqq (Aukelso/Bosaya), biosimilar, 1 mg (new code effective 04/01/26)
Q5162	Injection, denosumab-nxxp (Bildyos/Bilprevda), biosimilar, 1 mg (new code effective 04/01/26)
Q5165	Injection, denosumab-mobz (Oziltus), biosimilar, 1 mg (new code effective 07/01/26)

1–10 of 13

1/2

Benefit channel assignmentmixed

Bildyos (denosumab-nxxp)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Boncresa (denosumab-mobz)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Bosaya (denosumab-kyqq)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Conexxence (denosumab-bnht)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Enoby (denosumab-qbde)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Jubbonti (denosumab-bbdz)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Ospomyv (denosumab-dssb)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Osvyrti (denosumab-desu)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Prolia (denosumab)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit
Stoboclo (denosumab-bmwo)	administered subcutaneously every six months; managed through the medical benefit and pharmacy benefit

1–10 of 20

1/2

New HCPCS codesHCPCS

Q5161	New HCPCS code added (denosumab-kyqq / Aukelso/Bosaya) effective 04/01/26
Q5162	New HCPCS code added (denosumab-nxxp / Bildyos/Bilprevda) effective 04/01/26
Q5165	New HCPCS code added (denosumab-mobz / Oziltus) effective 07/01/26
Q5166	New HCPCS code added (denosumab-desu / Osvyrti/Jubereq) effective 07/01/26
Q5167	New HCPCS code added (denosumab-qbde / Enoby/Xtrenbo) effective 07/01/26
Q5171	New HCPCS code added (denosumab-mobz / Boncresa) effective 07/01/26

inv-08: approval duration by product group

Initial approval duration (oncology group)May be approved up to 6 months for Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo.

Initial/other product approvalBildyos, Boncresa, Bosaya, Conexxence, Enoby, Jubbonti, Ospomyv, Osvyrti, Prolia, and Stoboclo may be approved up to 2 years.

Renewal approval when stableNon-formulary exception reviews for select products may be approved up to 12 months when condition is stable and tolerated.

Extended approval with documentationCertain products (Bildyos, Boncresa, Bosaya, Conexxence, Enoby, Jubbonti, Ospomyv, Osvyrti, Prolia, Stoboclo) may be approved up to 2 years when chart notes show stabilization/improvement and no serious or intolerable side effects.

inv-09: SRE dosing limit

Provider Requirements and Prior Authorization

Documentation Required

Submit medical records with office visit notes and medication history

The individual's medical records must be submitted and should include office visit notes that contain the diagnosis and medication history to document that medical necessity criteria are met.

Include office visit notes with diagnosis and medication history

Step Therapy

Document inadequate response or intolerance to preferred products before non-preferred use

Non-preferred denosumab products require documentation that the individual had an inadequate response or intolerance to the specified preferred products before authorization will be granted.

For one group of non-preferred products: inadequate response/intolerance to Bildyos (denosumab-nxxp) AND Enoby (denosumab-qbde) is required.
For the other group of non-preferred products: inadequate response/intolerance to Bilprevda (denosumab-nxxp) AND Xtrenbo (denosumab-qbde) is required.

Definitions, Scope, and Benefit Application

inv-16: Denosumab — definition and mechanism

DefinitionDenosumab products are RANK ligand inhibitors used to reduce bone resorption and increase bone mass.

General classMonoclonal antibody class that inhibits RANK ligand to decrease osteoclast activity and bone turnover.

Clinical uses (summary)Used for osteoporosis, increasing bone mass with ADT or aromatase inhibitor therapy, prevention/treatment of skeletal-related events, hypercalcemia of malignancy, and giant cell tumor of bone as detailed in the policy.

inv-17: Policy introduction note

Purpose of policyDescribes when denosumab drugs may be considered medically necessary and informs providers about coverage criteria.

Audience note

Revision History and Policy Changes

2026-08-07policy_effective_dateLatest

Policy 5.01.658 became effective, consolidating prior policy content and applying updated coverage criteria including dose limits and product preference changes.

2026-07-01last_review

Policy last reviewed on July 1, 2026 (document shows last revised date).

2026-04-01coding_update

Policy Summary

PayerPremera Bluecross

PolicyDenosumab Products

Policy CodePolicy 5.01.658

Change TypeUpdated coverage criteria, product preference designations, dose limits, and coding additions

Effective DateAug 7, 2026

Last ReviewJul 1, 2026

Next Review DateAug 7, 2026

Key ActionSubmit medical records including office visit notes with diagnosis and medication history to document medical necessity.

SourceLink

On This Page

Conexxence (denosumab-bnht)

Jubbonti (denosumab-bbdz)

Ospomyv (denosumab-dssb)

Osvyrti (denosumab-desu)

Stoboclo (denosumab-bmwo)

Non‑preferred requiring prior trial of Bilprevda AND Xtrenbo

Aukelso (denosumab-kyqq)
Bomyntra (denosumab-bnht)
Jubereq (denosumab-desu)
Osenvelt (denosumab-bmwo)
Oziltus (denosumab-mobz)
Wyost (denosumab-bbdz)
Xbryk (denosumab-dssb)
Xgeva (denosumab)

ALL of the following

For prevention of skeletal‑related events in individuals with multiple myeloma and with bone metastases from solid tumors the dose is limited to 120 mg every 4 weeks

2026 changes included reclassification of several products to preferred or non‑preferred and updated step/criteria requiring trials of specified preferred products prior to approval

SRE prevention dose limitDose is limited to 120 mg every 4 weeks for prevention of skeletal-related events in individuals with multiple myeloma and with bone metastases from solid tumors.

Scope of applicationLimit applied across updated criteria for Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo.

Authorization useThis dosing limit should be applied in authorization decisions for SRE prevention indications.

inv-10: Dose limit for prevention of skeletal-related events

Dose limit (reiterated)For prevention of skeletal-related events in multiple myeloma and bone metastases from solid tumors the dose is limited to 120 mg every 4 weeks.

Products covered by limitApplied to Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo as noted in the 2026 update and history.

Effective/implementation notesDose-limiting language added in the 2026 update and reflected in policy history (07/01/26).

Billing Rule

Dose limited to 120 mg every 4 weeks for SRE prevention

For prevention of skeletal-related events in multiple myeloma and bone metastases, dosing is limited to 120 mg every 4 weeks; this dose limit must be applied in authorization decisions and reflected on claims.

Dose limit: 120 mg every 4 weeks for SRE prevention indications.
Apply this limit during prior authorization review and when adjudicating claims.

Prior Authorization

Expect updated prior authorization and coverage rules reflecting the 120 mg q4w limit

Coverage criteria and prior authorization rules were updated for multiple denosumab products; providers should expect the 120 mg every 4 weeks dose limit to be enforced for prevention of skeletal-related events in multiple myeloma and bone metastases.

Updated coverage criteria apply to Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo.
Expect revised prior authorization/coverage rules consistent with the added dose limit of 120 mg every 4 weeks.

Billing Rule

Use new HCPCS codes for denosumab billing per effective dates

New HCPCS codes were added for denosumab products; use the appropriate new codes for billing effective the listed dates.

New codes added effective 04/01/2026: Q5161, Q5162.
Additional new codes added effective 07/01/2026: Q5165, Q5166, Q5167, Q5171.
Include the appropriate HCPCS code on claims per the effective date in the policy history.

Introduction is informational only and not to be taken as coverage criteria; the rest of the policy uses clinical terminology intended for providers.

Basis for policyPolicies are developed from published literature, national guidelines, and standards of practice; member contracts determine actual benefits.

inv-18: Benefit Application

Benefit assignmentSome denosumab products administered subcutaneously every 6 months (e.g., Bildyos, Boncresa, Bosaya, Conexxence, Enoby, Jubbonti, Ospomyv, Osvyrti, Prolia, Stoboclo) are managed through both the medical and pharmacy benefits.

Medical benefit examplesAukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xgeva, and Xtrenbo are managed through the medical benefit.

Administration frequency tied to benefitProducts administered by a healthcare professional subcutaneously every six months are specifically noted for benefit channel assignment.

inv-19: Consideration of Age

Age determinationAge limits specified in this policy are determined according to FDA‑approved indications, where applicable.

Alignment with FDAPolicy references FDA labeling to set age restrictions for denosumab indications.

Provider responsibilityProviders should follow FDA‑approved age indications when documenting medical necessity for denosumab use.

inv-20: Denosumab products

Branded reference product(s)Prolia (denosumab) and Xgeva (denosumab) are listed as reference/branded products in the policy and references.

Biosimilars and branded biosimilarsAukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xtrenbo, Bildyos, Boncresa, Bosaya, Conexxence, Jubbonti, Ospomyv, Osvyrti, Stoboclo are referenced as branded or biosimilar products.

Policy history and product movementXgeva was moved into this policy from another policy and several products were reclassified to preferred or non-preferred status in the 2026 update and history.

New HCPCS codes Q5161 and Q5162 were added effective April 1, 2026 to support denosumab biosimilars.

2026-02-10interim_review

Interim review approved February 10, 2026 adding coverage criteria for Aukelso, Bosaya, Enoby, and Xtrenbo and updating J3590 parenthetical coding references.

2025-11-11interim_review

Interim review approved November 11, 2025 moved Xgeva from policy 5.01.540 into 5.01.658 and added coverage criteria for multiple denosumab products (Bildyos, Bilprevda, Bomyntra, Conexxence, Jubbonti, Osenvelt, Ospomyv, Stoboclo, Wyost, Xbryk).