Denosumab and Biosimilars (Prolia, Xgeva and biosimilars)
Criteria and authorization rules for denosumab (Prolia, Xgeva) and multiple biosimilars across osteoporosis and oncology indications for members of the payer lines of business listed.
Policy Summary
Payermhn
PolicyDenosumab and Biosimilars (Prolia, Xgeva and biosimilars)
Key ActionSubmit prior authorization with supporting clinical documentation demonstrating the member meets indication-specific criteria and any step-therapy or biosimilar preference requirements.
Added multiple new denosumab biosimilars and corresponding HCPCS codes to the policy.
Updated definition of very high risk for fracture and clarified bisphosphonate bypass criteria for osteoporosis.
Added boxed warning for severe hypocalcemia in patients with advanced kidney disease and indication-specific restrictions for oncology indications.
Modified oncology-related requirements and approval durations for Medicaid/HIM.
60 mgOsteoporosis max dose
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120 mgOncology max dose
12 monthsMedicaid/HIM duration
4New HCPCS codes added
NCApplicable state
boxed warningSafety change
Coverage Criteria and Indications
Initial Approval — Osteoporosis (Prolia-group)
Covered when ALL of the following are met:
Product: Request is for Prolia or specified Prolia-group biosimilars (e.g., Prolia, Bildyos, Boncresa, Bosaya, Conexxence, Enoby, Jubbonti, Ospomyv, Osvyrti, Stoboclo, denosumab-bnht, denosumab-dssb).
Diagnosis and risk: Diagnosis of postmenopausal osteoporosis (PMO), glucocorticoid‑induced osteoporosis (GIO), or male osteoporosis AND one of the following: (a) member is at very high risk for fracture as evidenced by (i) recent osteoporotic fracture within the past 12 months; (ii) BMD T‑score at hip or spine ≤ -3.0; or (iii) BMD T‑score at hip or spine ≤ -2.5 plus a major osteoporotic fracture; OR (b) member has completed a 3‑year trial of bisphosphonate therapy at up to maximally indicated doses (generic alendronate preferred) unless one of: all bisphosphonates are contraindicated; clinically significant adverse effects to both IV and PO formulations; loss of BMD while on bisphosphonate; lack of BMD increase after ≥12 months; or osteoporotic/fragility fracture while on bisphosphonate therapy.
See Appendix B/D for bisphosphonate specifics; bisphosphonate prior authorization may be required.
Age ≥ 18 years or documentation of closed epiphyses on x‑ray.
No concurrent oncology product: Prolia‑group product is not prescribed concurrently with Xgeva‑group (oncology) denosumab products.
Dose limit: Dose does not exceed 60 mg every 6 months.60 mg every 6 months
Initial Approval — Prostate/Breast Cancer Fracture Prevention (Prolia-group)
Covered when ALL of the following are met:
Product: Request is for Prolia or specified Prolia-group biosimilars (e.g., Prolia, Bildyos, Boncresa, Bosaya, Conexxence, Enoby, Jubbonti, Ospomyv, Osvyrti, Stoboclo, denosumab-bnht, denosumab-dssb).
Diagnosis and therapy: Diagnosis of prostate cancer receiving androgen deprivation therapy (ADT) OR breast cancer receiving adjuvant endocrine therapy (e.g., aromatase inhibitor); intended for fracture prevention.
No bone metastasis: Member does not have bone metastasis.
Prescriber: Prescribed by or in consultation with an oncologist.
Initial Approval — Multiple Myeloma or Solid Tumor (Xgeva-group)
Covered when ALL of the following are met:
Product: Request is for Xgeva or specified Xgeva‑group biosimilars (e.g., Xgeva, Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xtrenbo, denosumab‑bnht).
Diagnosis of multiple myeloma OR bone metastasis secondary to a solid tumor.
Prescriber: Prescribed by or in consultation with an oncologist.
Age ≥ 18 years or documentation of closed epiphyses on x‑ray.
Prior therapy/step: For indications other than prostate or breast cancer, member must have failed zoledronic acid or pamidronate at maximally indicated doses unless clinically significant adverse effects or contraindications exist; or a state regulation exception to step therapy applies.
Initial Approval — Giant Cell Tumor of Bone (Xgeva-group)
Covered when ALL of the following are met:
Product: Request is for Xgeva or specified Xgeva‑group biosimilars (e.g., Xgeva, Aukelso, Bilprevda, Bomyntra, Jubereq, Osenvelt, Oziltus, Wyost, Xbryk, Xtrenbo, denosumab‑bnht).
Disease characterization: Diagnosis of giant cell tumor of bone that is characterized as: (a) metastatic or unresectable; OR (b) localized disease prescribed as single agent or with serial embolization and/or radiation; OR (c) resectable disease where surgical resection is likely to result in severe morbidity.
Prescriber: Prescribed by or in consultation with an oncologist.
Age ≥ 18 years or documentation of closed epiphyses on x‑ray.
Giant Cell Tumor of Bone - initial/continuation
Giant Cell Tumor of Bone (must meet all):
Giant cell tumor of bone criteria: Dose does not exceed 120 mg every 4 weeks plus 120 mg on days 8 and 15 of the first month of therapy.see dosing
Must meet all requirements in section (prescriber, age, product selection rules, no concurrent Prolia‑group use).
Hypercalcemia of Malignancy
Hypercalcemia of Malignancy (must meet all):
Hypercalcemia of malignancy criteria: Request is for an Xgeva‑group product; diagnosis of hypercalcemia of malignancy; prescribed by or in consultation with an oncologist; age ≥ 18 years or documentation of closed epiphyses on x‑ray; albumin‑corrected calcium > 12.5 mg/dL despite IV bisphosphonate therapy within the last 30 days.albumin‑corrected Ca > 12.5 mg/dL
Prior authorization may be required; biosimilar‑first requirements (Bilprevda, Osenvelt, Wyost) apply unless exceptions met.
Systemic mastocytosis criteria: Request is for an Xgeva‑group product; diagnosis of systemic mastocytosis with osteopenia or osteoporosis and bone pain; prescribed by or in consultation with an oncologist; age ≥ 18 years or documentation of closed epiphyses on x‑ray; member has failed zoledronic acid or pamidronate at maximally indicated doses unless clinically significant adverse effects or contraindicated OR request is for treatment associated with cancer in a State with regulations against step therapy; if product is other than Bilprevda/Osenvelt/Wyost, those preferred biosimilars must be used first unless clinically significant adverse effects/all contraindicated or state rules prohibit step therapy; dose is within FDA maximum for any FDA‑approved indication or is supported by practice guidelines/peer‑reviewed literature and prescriber must submit supporting evidence; prescribed regimen must be FDA‑approved or recommended by NCCN.FDA maximum or guideline‑supported
Prescriber must provide supporting evidence for off‑label dosing; prior authorization may be required.
Continuation Therapy
Continuation Therapy / All Indications in Section I (must meet all):
Continuation criteria: Member currently receiving medication via Centene benefit or previously met initial approval criteria; or member is covered by continuity of care rules; or documentation that member has been receiving listed denosumab products for a covered cancer‑related indication for at least 30 days; member is responding positively to therapy; if request is for a dose increase, new dose must not exceed product‑specific maximums (Prolia‑class 60 mg every 6 months; Xgeva‑class 120 mg every 4 weeks unless guideline‑supported off‑label dosing with evidence).product‑specific dose limits
Prescribed regimen must be FDA‑approved or recommended by NCCN; approval durations vary by line of business.
Other/Not-Specified Indications
Other diagnoses/indications (coverage decision pathway):
Other indications path: If the drug recently (within 6 months) had a label change not yet reflected in this policy, follow the applicable formulary/no‑coverage or non‑formulary policy for the relevant line of business; if the requested use is not specifically listed and no recent label change applies, refer to the off‑label use policy for the relevant line of business (see referenced payer policies).referenced policies apply
Covered when criteria for indication, dosing, and safety evaluation are met
Osteoporosis indications: Denosumab (Prolia and biosimilars) covered for postmenopausal osteoporosis, glucocorticoid‑induced osteoporosis, and male osteoporosis at 60 mg subcutaneous every 6 months.
See dosing reference.
Oncology indications: Denosumab (Xgeva and biosimilars) covered for prevention of skeletal‑related events in bone metastases, hypercalcemia of malignancy, and giant cell tumor of bone at 120 mg subcutaneous every 4 weeks (with additional 120 mg doses on days 8 and 15 of the first month for some indications).
See dosing reference.
Safety preconditions: Patients must not have hypocalcemia or known clinically significant hypersensitivity to denosumab products; patients with advanced chronic kidney disease require evaluation for CKD‑MBD and supervision by a provider experienced in CKD‑MBD prior to initiating Prolia‑class products.
Boxed warnings and safety notes updated in recent reviews.
Osteoporosis: initial therapy revisions
Policy-level clinical criteria were updated in recent annual reviews for osteoporosis and other indications.
Osteoporosis updates: Updated definition of very high risk for fracture per 2020 AACE/ACE PMO guidelines; added option to bypass bisphosphonate trial if member experienced loss of BMD, lack of BMD increase, or had an osteoporotic/fragility fracture while receiving bisphosphonate therapy; clarified preference that failure of generic alendronate is preferred.
1Q2022 and 1Q2024 updates.
Oncology and other specialty indications
Oncology and other specialized indications had product- and safety-specific changes.
Safety and indication-specific restrictions: Added boxed warning for severe hypocalcemia in patients with advanced kidney disease for Prolia and certain biosimilars; for prostate and breast cancer added requirement that member does not have bone metastasis; for giant cell tumor of bone removed option for combination use with interferon alfa for localized disease per NCCN and added resectable‑disease pathway when surgery likely causes severe morbidity.
Changes from 1Q2025 and 1Q2026 reviews.
Oncology therapy initiation and duration: For multiple myeloma, removed requirement that member be receiving or initiating therapy for symptomatic disease; Medicaid/HIM initial approval duration for oncology indications revised from 6 to 12 months.
1Q2026 annual review.
Biosimilar preference and redirection
Biosimilar product routing and preference.
Product redirection/preference: For multiple myeloma, solid tumor, giant cell tumor of bone, hypercalcemia of malignancy, and systemic mastocytosis, requests for products other than Osenvelt and Wyost may be redirected to Osenvelt and Wyost for initial and continuation therapy; Bilprevda and other biosimilars are listed as preferred in updates.
Per August and December SDC and RT4 updates.
Diagnoses and indications for which coverage is NOT authorized are listed in Section III of the policy. Refer to that section when a requested use is not described among the approved indications and pathways elsewhere in this document.
Uses that are not FDA‑approved and are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid) or other evidence of coverage documents.
The policy lists common contraindications and adverse effects for oral and IV bisphosphonates that may support bypassing a bisphosphonate trial. Examples include inability to sit/stand upright for ≥30 minutes (oral agents), hypocalcemia, pregnancy, clinically significant hypersensitivity, acute renal failure or creatinine clearance <35 mL/min for IV formulations, osteonecrosis of the jaw, atypical femoral fracture, and severe musculoskeletal pain. These documented contraindications or adverse effects may be used to justify use of denosumab when the bisphosphonate trial requirement is inapplicable.
For the prostate and breast cancer fracture‑prevention pathway the policy requires that the member does not have bone metastasis; presence of bone metastasis excludes the Prolia‑group approval pathway and redirects consideration to oncology dosing/products (Xgeva‑group) and related criteria.
The policy explicitly prohibits concurrent use of products from the Prolia‑group with products from the Xgeva‑group. Requests where a Prolia‑class product is prescribed at the same time as an Xgeva‑class product are not authorized and may be denied.
Off‑label or non‑FDA‑approved uses that are not addressed within this policy are considered not authorized unless the prescriber provides documentation meeting the plan’s off‑label use requirements. In addition, inclusion of procedure or HCPCS codes in this document is for informational purposes only and does not by itself establish medical necessity for an off‑label request.
The HCPCS and other billing codes listed in this policy are provided for informational use only. Inclusion of a code does not guarantee that a claim will be covered; providers must ensure the clinical criteria in this policy are met and follow current professional coding guidance when submitting claims.
Codes referenced in this clinical policy (for example, J0897 and the denosumab biosimilar Q‑codes) are intended to help identify the product for prior authorization and claims processing. They are informational and do not alone establish coverage — authorizations are based on meeting the clinical criteria in the policy.
RequirementAge ≥ 18 years or documentation of closed epiphyses on x-ray.
Applies toInitial approval for osteoporosis and many oncology-related indications where skeletal maturity is required.
Source noteSpecified in initial approval criteria for Prolia-group and reiterated in general coverage rules.
Albumin-corrected calcium
ThresholdAlbumin-corrected calcium > 12.5 mg/dL.
ContextRequired for Hypercalcemia of Malignancy after IV bisphosphonate therapy within prior 30 days.
Prior Authorization, Documentation and Operational Rules
Prior Authorization
Prior authorization and step therapy for oncology-related indications
Prior authorization is required for oncology-related indications (multiple myeloma, bone metastasis from solid tumor, giant cell tumor of bone, hypercalcemia of malignancy, and systemic mastocytosis) and may include state-specific step therapy exceptions. Requests for these indications must be prescribed by or in consultation with an oncologist and meet the policy-specific clinical criteria. For Illinois HIM requests, certain step therapy requirements do not apply as specified in Appendix E and per IL HB 5395.
Oncology indications require prior authorization and adherence to step therapy unless state law (eg, IL HB 5395) or Appendix E provides an exception.
Prescriber requirement: oncologist or consultation with an oncologist for oncology-related indications.
Step Therapy
Biosimilar-first requirement in specified oncology settings
Some approvals require that the member try and fail specified biosimilars before non-preferred products are approved (biosimilar-first requirement) in certain oncology settings unless clinically significant adverse effects occur or all preferred biosimilars are contraindicated. For Illinois HIM requests, the biosimilar-first/step therapy requirements may not apply as noted (unless a biosimilar is FDA-designated interchangeable).
Initial therapy requirements for specified oncologic/related conditions
Initial hypercalcemia of malignancy: Request is for an Xgeva‑group product; diagnosis of hypercalcemia of malignancy; prescribed by or in consultation with an oncologist; age ≥ 18 years or documentation of closed epiphyses on x‑ray; albumin‑corrected calcium > 12.5 mg/dL despite IV bisphosphonate therapy within the last 30 days; biosimilar‑first requirement applies unless exceptions met.
Prior authorization may be required.
Initial systemic mastocytosis: Request is for an Xgeva‑group product for systemic mastocytosis with osteopenia/osteoporosis and bone pain; prescribed by or in consultation with an oncologist; age ≥ 18 years or documentation of closed epiphyses on x‑ray; prior failure of zoledronic acid or pamidronate at maximally indicated doses unless contraindicated or adverse effects; if using off‑label dosing, prescriber must submit supporting evidence that dosing is within FDA maximum or supported by practice guidelines/peer‑reviewed literature.
Prescribed regimen must be FDA‑approved or NCCN‑recommended where applicable.
Continuation and Renewal Requirements
Continuation Therapy
Continuation/renewal requirements
Continuation: Member currently receiving medication via Centene benefit or previously met initial approval criteria, or member is covered by continuity of care rules, or documentation supports at least 30 days of therapy for a covered cancer‑related indication; member is responding positively to therapy.
If request is for a dose increase, new dose must not exceed product‑specific maximums.
Continued therapy
Continuation and monitoring
Continued therapy considerations: Continued therapy should follow initial indication dosing intervals and include monitoring for hypocalcemia and renal‑related risk factors; treat continuation requests consistent with policy template and annual review updates.
See 1Q2022–1Q2024 template and monitoring updates.
Step Therapy Requirements and Preferred Products
Requirement
Documentation needed
Members must have prior use/failure of required prior agents or a documented contraindication to those agents
Office chart notes, prior medication records showing bisphosphonate/zoledronic acid/pamidronate use and dates, reason for failure or adverse effect, or documentation of contraindication
For osteoporosis indications: completion of a 3-year trial of bisphosphonate therapy is generally expected unless bypass criteria met (contraindication, adverse effects, loss of BMD, lack of BMD increase after ≥12 months, or fracture while on therapy)
BMD reports (T-scores), treatment timelines showing bisphosphonate duration, serial BMD results demonstrating loss or lack of increase, fracture history documentation
For oncology-related indications: failure of zoledronic acid or pamidronate at maximally indicated doses is required unless contraindicated or adverse effects; state regulations may override step therapy (e.g., Illinois HIM)
Records of zoledronic acid or pamidronate administration and response/adverse effects, or documentation of state-specific exception (Appendix E) when applicable
Failure to submit supporting clinical documentation may result in denial
Any relevant labs, imaging, prescriber notes, and prior authorization forms demonstrating criteria have been met
Step therapy rule
Scope / exceptions
Member must use Bilprevda, Osenvelt, and Wyost before other denosumab products for specified oncology-associated conditions
Applies to multiple myeloma, bone metastasis, giant cell tumor of bone, hypercalcemia of malignancy, systemic mastocytosis and other oncology-related indications unless clinically significant adverse effects or contraindications to all three
If request is for a product other than Bilprevda, Osenvelt, and Wyost, those three must be used first unless all are contraindicated or cause clinically significant adverse effects
Documentation of adverse effects/contraindications to preferred biosimilars required; state regulations against step therapy (see Appendix E) may exempt the member
Step therapy requirements do not apply for Illinois HIM requests as of 1/1/2026 per IL HB 5395 (unless biosimilar is interchangeable per FDA Purple Book)
Reference to IL HB 5395 or payer addendum; indicate biosimilar interchangeability when applicable
Continuation requests for oncology indications also subject to redirection to Osenvelt/Wyost/Bilprevda where applicable
Clinical notes showing prior use of preferred biosimilars or rationale for exception; see continuation criteria for redirection rules
Osteoporosis step requirement
Bypass / acceptable alternatives
Preferred: trial of oral or IV bisphosphonate (generic alendronate preferred) prior to denosumab for osteoporosis initial therapy
Medication history documenting a 3-year bisphosphonate trial at maximally indicated doses (or documentation that generic alendronate was tried and failed)
Bypass allowed if member meets any of: all bisphosphonates contraindicated; clinically significant adverse effects to both IV and PO formulations; loss of BMD while on bisphosphonate; lack of BMD increase after ≥12 months; or osteoporotic/fragility fracture while on bisphosphonate
Clinical documentation of contraindication, adverse events (per Appendix D), serial BMD results showing loss or no increase, or fracture records while on therapy
When bisphosphonate trial is bypassed, prescriber rationale and supporting evidence must be provided
Office notes explaining reason for bypass and supportive labs/imaging or specialist consultation notes
State variation
Effect on step therapy
Illinois (HIM): step therapy bypass added per IL HB 5395; step therapy requirements do not apply for Illinois HIM requests as of 1/1/2026
Reference IL HB 5395 or payer-specific HIM addendum; documentation of member's HIM status may be required
States with regulations against oncology step therapy (see Appendix E) may exempt members from step requirements
Provide state-specific regulatory documentation or indicate treatment is 'associated with cancer' in a state listed in Appendix E
When state exceptions apply, standard biosimilar-first or bisphosphonate-first requirements may be waived
Documentation of the applicable state regulation or payer addendum demonstrating the exemption
IndicationOncology indications (multiple myeloma, solid tumor bone metastases, giant cell tumor of bone, hypercalcemia of malignancy).
Administration Setting and Formulation Notes
Note
Match administration setting to formulation
Product formulations are available as single‑use prefilled syringes or vials; administer in an appropriate setting (office or infusion center) consistent with the product presentation and clinical need.
Select administration site consistent with product formulation (e.g., 60 mg prefilled syringe vs 120 mg vial).
Note
Infusion center guidance (no site‑of‑care limits in excerpt)
No site‑of‑care limits are specified in the provided excerpt; follow usual denosumab administration practices and Health Plan procedural requirements for infusion center use.
Biosimilar Preferences and Redirection
Billing Rule
Use Bilprevda/Osenvelt/Wyost before other oncology products
For Xgeva‑group oncology indications, the policy requires use of Bilprevda, Osenvelt, and Wyost before other denosumab products when available unless clinically significant adverse effects or contraindications exist.
Billing Rule
Preferred‑biosimilar first requirement for oncology uses
For other denosumab products used in specified oncology settings, members must use Bilprevda, Osenvelt, and Wyost prior to non‑preferred products unless all three are contraindicated, produce clinically significant adverse effects, or state rules prohibit step therapy.
Billing Rule
Biosimilars and Q‑codes (list provided)
Background and Scope
Denosumab is a RANK‑ligand inhibitor used to reduce fracture risk in osteoporosis and to prevent or treat skeletal‑related complications of malignancy. Product dosing and indications differ by formulation: Prolia‑class products (e.g., Prolia and listed biosimilars) are indicated for osteoporosis/ fracture prevention and are dosed at 60 mg subcutaneously every 6 months, whereas Xgeva‑class products (higher‑dose denosumab and specified biosimilars) are used for oncology indications (bone metastases, multiple myeloma, giant cell tumor of bone, hypercalcemia of malignancy) and are dosed at 120 mg subcutaneously every 4 weeks with additional loading doses on days 8 and 15 of the first month for some indications.
Definitions and Abbreviations
High risk of fracture
DefinitionHistory of osteoporotic fracture, multiple risk factors for fracture, or failure/intolerance to other available osteoporosis therapy.
UsesDefines patients eligible for high-risk osteoporosis indications (PMO, male osteoporosis, GIO).
Policy note'Very high risk' definition updated per 2020 AACE/ACE PMO guidelines (see annual review notes).
BMD
TermBMD = bone mineral density.
T-score useBMD T-score is used for diagnosis; T-score ≤ -2.5 indicates osteoporosis; WHO defines normal as -1.0 or above.
Appendix reference
Policy Summary
Payermhn
PolicyDenosumab and Biosimilars (Prolia, Xgeva and biosimilars)
Key ActionSubmit prior authorization with supporting clinical documentation demonstrating the member meets indication-specific criteria and any step-therapy or biosimilar preference requirements.
Prior therapy/step: Member meets one of: (a) for breast cancer, failure of zoledronic acid or pamidronate at maximally indicated doses unless clinically significant adverse effects or contraindicated; (b) for prostate cancer, failure of zoledronic acid at maximally indicated doses unless clinically significant adverse effects or contraindicated; OR (c) state regulation exception to step therapy applies (e.g., Illinois HIM per IL HB 5395).
Prior authorization may be required for prior agents.
No concurrent oncology product: Prolia‑group product is not prescribed concurrently with Xgeva‑group products.
Dose limit: Dose does not exceed 60 mg every 6 months.60 mg every 6 months
Product selection rule: If request is for a product other than Bilprevda, Osenvelt, and Wyost, member must use those three unless clinically significant adverse effects, all are contraindicated, or state exception applies.
No concurrent osteoporosis product: Xgeva‑group products are not prescribed concurrently with Prolia‑group products.
Dose limit: Dose does not exceed 120 mg every 4 weeks.120 mg every 4 weeks
Product selection rule:
If request is for a product other than Bilprevda, Osenvelt, and Wyost, member must use Bilprevda, Osenvelt, and Wyost unless clinically significant adverse effects, all are contraindicated, or state exception applies.
No concurrent osteoporosis product: Xgeva‑group products are not prescribed concurrently with Prolia‑group products.
Dose limit initial month: Dose does not exceed 120 mg every 4 weeks plus 120 mg on days 8 and 15 of the first month of therapy.120 mg every 4 weeks plus 120 mg on days 8 and 15 first month
Bypass bisphosphonate trial: For osteoporosis, a bisphosphonate trial may be bypassed if member has contraindications/adverse effects to bisphosphonates or has experienced loss of BMD, lack of BMD increase, or sustained an osteoporotic/fragility fracture while receiving bisphosphonate therapy.
Policy amendment noted in coding implications (1Q2022 and 1Q2024 updates).
Prior auth notePrior authorization may be required for this indication.
Oncologic dosing limit
Maximum oncology dosing120 mg every 4 weeks.
Giant cell tumor loadingPlus 120 mg on days 8 and 15 of the first month of therapy when indicated.
Concurrent product ruleXgeva-group (oncology) products must not be prescribed concurrently with Prolia-group products.
Prolia-class dosing limit (osteoporosis)
Maximum osteoporosis dosing60 mg every 6 months.
No concurrent oncology productProlia-group products are not prescribed concurrently with Xgeva-group products.
Dose increase capIf request is for a dose increase, new dose must not exceed 60 mg every 6 months for Prolia-class products.
Dosing regimens
Prolia regimen60 mg subcutaneous once every 6 months.
Xgeva/oncology regimen120 mg subcutaneous once every 4 weeks; some indications require additional 120 mg doses on days 8 and 15 of the first month.
Approval durationsTypical approval durations: Medicaid/HIM 12 months; Commercial 6 months (or to member renewal date).
In multiple myeloma, giant cell tumor of bone, hypercalcemia of malignancy, systemic mastocytosis, and other oncology indications: member must use Bilprevda, Osenvelt, and Wyost (or other specified preferred biosimilars) unless contraindicated or clinically significant adverse effects are experienced.
Illinois HIM: step therapy/biosimilar-first bypass applies per IL HB 5395; interchangeability per FDA Purple Book may affect applicability.
Billing Rule
Coding-linked prior auth
Certain drug- and diagnosis-specific coding triggers prior authorization screening. Providers must submit the appropriate HCPCS/J-codes on requests and claims, and be aware that coding may trigger clinical review.
Coding on the request may be used to route to the appropriate clinical criteria and prior authorization workflow.
Documentation Required
Documentation requirement
Providers must submit supporting clinical documentation with prior authorization requests. Acceptable documentation includes office chart notes, relevant laboratory results (including albumin-corrected calcium and renal function), imaging reports (e.g., DXA showing BMD/T-score), and documentation of prior therapies and responses or adverse events.
Documentation must show diagnosis, age/closed epiphyses, prior bisphosphonate trial or documented bypass reason, and evidence of fracture risk or metastasis when applicable.
For off-label uses (eg, systemic mastocytosis) prescriber must submit supporting evidence from practice guidelines or peer-reviewed literature if regimen is outside FDA-approved dosing.
Denial Risk
Concurrent product conflict
Providers must include drug history demonstrating trials and responses to bisphosphonates or preferred biosimilars when applicable. Concurrent prescribing of denosumab products intended for different indications is not allowed and will be a basis for denial.
Products intended for osteoporosis (Prolia, biosimilars for Prolia) must not be prescribed concurrently with oncology-targeted denosumab products (Xgeva and listed biosimilars) and vice versa.
Concurrent product combinations that are explicitly disallowed will trigger denial (see policy drug lists).
Denial Risk
Denial triggers
Prior authorization may be denied if required clinical criteria or documentation are missing, if concurrent disallowed products are prescribed, if dosing exceeds policy limits, or if step therapy requirements are not met and no allowable bypass reason is documented.
Denial triggers include: missing supporting clinical documentation; concurrent use of disallowed denosumab products; doses exceeding 60 mg every 6 months for osteoporosis products or 120 mg every 4 weeks for oncology products (unless supported by guidelines for off-label use); failure to meet step therapy requirements without documented contraindication or adverse effects.
Requests for dose increases that exceed policy-specified maximums will be denied unless supported by guideline or literature evidence submitted by the prescriber.
Denial Risk
Contraindication: hypocalcemia / hypersensitivity
Denosumab products are contraindicated in patients with hypocalcemia and in patients with known clinically significant hypersensitivity to denosumab products. Advanced CKD increases the risk of severe hypocalcemia and requires special evaluation prior to initiation.
Do not initiate denosumab in patients with untreated hypocalcemia; correct serum calcium prior to dosing.
Known hypersensitivity to denosumab products is a contraindication.
Patients with advanced CKD should be evaluated for CKD-MBD and therapy should be supervised by a clinician experienced in CKD-MBD management.
Documentation Required
Coding does not guarantee coverage
Coding references in this policy are informational; inclusion or exclusion of a code does not guarantee coverage. Providers must follow current professional coding guidance when submitting claims.
Codes listed (eg, J0897, Q5136, Q5157, Q5158, Q5159) are for reference only and do not ensure payment.
Providers should verify coding and modifiers with the latest coding manuals and payer billing guidance before claim submission.
Documentation Required
Required supporting clinical documentation
Required supporting clinical documentation for initial and continued approval includes evidence of diagnosis, prior therapies and response/adverse effects (including bisphosphonate trial details or reasons for bypass), DXA/BMD results, fracture history, oncology treatment context when applicable, lab results including albumin-corrected calcium and renal function, and prescriber specialty documentation when an oncologist’s involvement is required.
For osteoporosis: documentation of a 3-year bisphosphonate trial is required unless bypass criteria met (contraindication, adverse effects to IV and PO, loss of BMD while on bisphosphonate, lack of BMD increase after ≥12 months, or fracture while on bisphosphonate).
For oncology and off-label indications: submit documentation of prior IV bisphosphonate use or preferred biosimilar trials where required, and any supporting literature for off-label regimens.
Documentation Required
CKD-MBD evaluation and specialist supervision
Patients with advanced chronic kidney disease require evaluation for CKD–MBD before initiating Prolia and related osteoporosis denosumab products. Treatment in these patients should be managed or supervised by a clinician with expertise in CKD–MBD due to increased risk of severe hypocalcemia.
Obtain and document assessment for CKD–MBD and baseline calcium and renal function prior to therapy.
Specialist supervision (nephrology or clinician experienced in CKD–MBD) is recommended for initiation and monitoring in advanced CKD.
Documentation Required
Coding and documentation
Providers should attach copies of relevant imaging and lab reports, calculate and document albumin-corrected calcium when applicable, and include specific drug names, doses, dates, and reasons for prior therapy discontinuation or failure. Documentation supporting off-label use must include guideline or peer-reviewed literature citations when the regimen is not FDA-approved.
Include DXA reports with T-scores, fracture dates and descriptions, and prior bisphosphonate or bisphosphonate-bypass rationale.
For dose increases or off-label regimens, include practice guideline (eg, NCCN) or peer-reviewed literature supporting the requested regimen.
Step Therapy
Step therapy / prior bisphosphonate requirement
Step therapy for osteoporosis generally requires a trial of bisphosphonate therapy (generic alendronate preferred) for 3 years at maximally indicated doses unless bypass criteria are met (contraindication, adverse effects to both IV and PO bisphosphonates, loss of BMD while on therapy, lack of BMD increase after ≥12 months, or fracture while on therapy). Prior authorization may be required for bisphosphonates.
Bisphosphonate trial: 3 years of therapy documented, with dates, dose, and evidence of adherence.
Bypass allowed when any of the specified clinical exceptions are documented; providers must submit supporting evidence.
Step Therapy
Bisphosphonate trial / bypass
When a bisphosphonate trial is required but cannot be completed due to contraindication, intolerance, or specific clinical failure (loss of BMD, lack of BMD gain, or fracture while on therapy), providers should document the reason to request bypass of the bisphosphonate trial.
Acceptable bypass reasons include: all bisphosphonates contraindicated; clinically significant adverse effects to both IV and PO formulations; loss of BMD while on bisphosphonate therapy; lack of BMD increase after ≥12 months; or osteoporotic/fragility fracture while receiving bisphosphonate therapy.
Provide chart notes, adverse event documentation, and relevant lab/imaging to support bypass request.
Initial therapy dosing
Initial dosing by indication
Osteoporosis initial dosing: Prolia‑class dosing: 60 mg subcutaneous once every 6 months for PMO, GIO, and male osteoporosis.
See V. Dosage and Administration.
Oncology initial dosing: Xgeva‑class dosing: 120 mg subcutaneous once every 4 weeks for oncology indications; for certain indications (e.g., giant cell tumor of bone, hypercalcemia of malignancy) additional 120 mg doses on days 8 and 15 of the first month are required.
See V. Dosage and Administration and indication sections.
Initial therapy criteria (selected)
Initial therapy criteria were updated to reflect fracture risk definitions and biosimilar additions.
Osteoporosis initial: Very high fracture risk definition updated per 2020 AACE/ACE PMO guidelines; bisphosphonate trial may be bypassed for osteoporosis when member has loss of BMD, lack of BMD increase, or sustained an osteoporotic/fragility fracture while on bisphosphonate therapy; clarified preference for failure of generic alendronate.
1Q2022 and 1Q2024 updates; new biosimilars added in RT4 updates.
Continuation therapy redirection
Product redirection applies to both initial and continuation therapy in specified oncology and related indications.
Continuation redirection: Continuation therapy requests for certain malignancy‑related indications (multiple myeloma, solid tumor bone metastasis, giant cell tumor of bone, hypercalcemia of malignancy, systemic mastocytosis) may be redirected to preferred biosimilars (e.g., Osenvelt, Wyost; Bilprevda added as preferred per updates) for initial and continuation therapy unless clinically significant adverse effects, contraindication, or state regulation exception applies.
Per August SDC and subsequent RT4 updates.
Key actionable limitDose does not exceed 120 mg every 4 weeks (with additional loading doses in month 1 for some indications).
Xgeva and specified biosimilars dosing
Oncology dosing (hypercalcemia)120 mg every 4 weeks plus 120 mg on days 8 and 15 of first month when indicated.
Biosimilar preferenceIf request is for a product other than Bilprevda, Osenvelt, and Wyost, member must use those three unless clinically significant adverse effects or contraindications exist or state rules prohibit step therapy.
Prior authPrior authorization may be required and step therapy/biosimilar-first rules apply to many oncology settings.
Prolia and listed biosimilars dosing
Prolia-class dosing60 mg every 6 months for osteoporosis indications.
No concurrent oncology productProlia-group products must not be prescribed concurrently with Xgeva-group products.
Biosimilars listedMultiple Prolia-class biosimilars are included in criteria and subject to the same dosing limits.
Biosimilar products are listed with specific product names and corresponding Q‑codes; include the appropriate Q‑code (e.g., Q5136, Q5157, Q5158, Q5159) for biosimilars when submitting claims or authorizations.
Billing Rule
Oncology product routing: redirection to preferred biosimilars
For oncology indications (multiple myeloma, solid tumor bone metastasis, giant cell tumor of bone, hypercalcemia of malignancy, systemic mastocytosis), product requests other than the preferred biosimilars may be redirected to Osenvelt and Wyost for initial and continuation therapy.
Redirection to Osenvelt and Wyost applies to both initial and continuation requests per the August SDC.
Billing Rule
Added preferred biosimilar (Bilprevda)
A preferred biosimilar (Bilprevda) was added to the policy per the December SDC; providers should expect Bilprevda to be treated as an additional preferred option in specified oncology and continuation pathways.
See Appendix F for interpretation of T-scores and related guidance.
CKD-MBD
TermCKD-MBD = chronic kidney disease–mineral bone disorder.
Evaluation requirementPatients with advanced CKD must be evaluated for CKD‑MBD and treatment supervised by a provider experienced in CKD‑MBD prior to initiating Prolia or specified biosimilars.
Safety noteBoxed warning added for severe hypocalcemia in patients with advanced kidney disease (per 1Q2025 updates).
BMD T-score definition
DefinitionBMD T-score = number of standard deviations an individual's BMD is from mean for young normal women.
WHO thresholdsNormal: T-score ≥ -1.0; Osteoporosis: T-score ≤ -2.5 (severe osteoporosis with fragility fracture).
Clinical useT-score is an operational definition for diagnosis of postmenopausal osteoporosis per WHO and guideline references.
Very high risk for fracture (definition updated — full text elsewhere)
Update summary'Very high risk for fracture' definition revised based on 2020 AACE/ACE PMO guidelines.
Policy impactAllows bisphosphonate trial bypass for osteoporosis in cases of BMD loss, lack of BMD increase, or fracture while on therapy.
ReferenceSee full definition text elsewhere in the policy (Appendix/criteria sections).