CurrentCignaPolicy IP0745

Colony Stimulating Factors - Ryzneuta (efbemalenograstim) coverage criteria

Defines prior authorization, coverage criteria, dosing, and limitations for Ryzneuta (efbemalenograstim alfa-vuxw) for Cigna-administered health benefit plans, affecting prescribers and providers requesting coverage.

Policy Summary

PayerCigna

PolicyColony Stimulating Factors - Ryzneuta (efbemalenograstim) coverage criteria

Policy CodePolicy IP0745

Change TypeNew policy with material clinical and coverage additions

Effective Date

Next Review Date

Key ActionObtain prior authorization and document that the patient meets the specified clinical criteria and dosing limits before coverage is approved.

SourceLink

POLICY UPDATE CHANGES

New policy created for Ryzneuta; added clinical criteria and dosing for cancer patients receiving myelosuppressive chemotherapy and for hematopoietic acute radiation syndrome.

Updated criteria language from 'Non-myeloid malignancy receiving myelosuppressive chemotherapy associated with an increased risk of febrile neutropenia' to 'Cancer in a Patient Receiving Myelosuppressive Chemotherapy.'

Employer and Individual/Family plan-specific step/preferred product requirements for use of Ryzneuta relative to pegfilgrastim and Rolvedon.

A new dosing limitation was added: approve up to 20 mg subcutaneous no more frequently than once every 2 weeks for the cancer indication; for H-ARS, two doses up to 20 mg one week apart.

20 mgmaximum single dose (SC)

6 monthscancer approval duration

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Coverage Criteria for Ryzneuta (efbemalenograstim)

Initial therapy - cancer

Ryzneuta is considered medically necessary when ONE of the following is met. FDA-Approved Indication: Cancer in a Patient Receiving Myelosuppressive Chemotherapy. Approve for 6 months if the patient meets ALL of the following:

Cancer in a Patient Receiving Myelosuppressive Chemotherapy

Patient meets ONE of the following (i, ii, or iii)
- i): Patient is receiving myelosuppressive anti-cancer medications that are associated with a high risk of febrile neutropenia (the risk is at least 20% based on the chemotherapy regimen).
- ii)
  - a): Patient is receiving myelosuppressive anti-cancer medications that are associated with a risk of febrile neutropenia, but the risk is less than 20% based on the chemotherapy regimen.
  - b): Patient has at least ONE risk factor for febrile neutropenia according to the prescriber (examples include age > 65 years receiving full chemotherapy dose intensity; prior chemotherapy or radiation therapy; persistent neutropenia; bone marrow involvement by tumor; recent surgery and/or open wounds; liver dysfunction [bilirubin > 2.0 mg/dL]; renal dysfunction [creatinine clearance < 50 mL/min]; poor performance status; HIV infection with low CD4 counts).
- iii)
  - a): Patient has had a neutropenic complication from a prior chemotherapy cycle and did not receive prophylaxis with a colony stimulating factor (examples include filgrastim products, pegfilgrastim products, Rolvedon [eflapegrastim-xnst subcutaneous injection]).
  - b): A reduced dose or frequency of chemotherapy may compromise treatment outcome.
Additional required conditions
- C) The medication is prescribed by or in consultation with an oncologist or hematologist.
- D) Preferred product criteria are met as listed in the policy (plan-specific step/preferred product requirements).

H-ARS

Radiation Syndrome (Hematopoietic Syndrome of Acute Radiation Syndrome) — Approve for 1 month if BOTH are met:

Dosing: Approve two doses of up to 20 mg by subcutaneous injection no more frequently than 1 week apart. Definitive dosing has not been established for Ryzneuta in H-ARS; Neulasta labeling recommends two subcutaneous doses one week apart.

Ryzneuta is not medically necessary when used for indications outside the specified coverage criteria. In particular, Ryzneuta is not indicated for mobilization of peripheral blood progenitor cells (PBPCs) for hematopoietic stem cell transplantation and such use will be considered not medically necessary. This exclusion is consistent with the product’s limitation of use and applies regardless of patient age or treatment setting.

The policy’s list of not-covered conditions is not exhaustive and may be updated as new evidence becomes available; however, any use of Ryzneuta that does not meet the policy’s defined indications (cancer prophylaxis for febrile neutropenia or Hematopoietic Acute Radiation Syndrome per the coverage criteria) should be expected to be denied as not medically necessary.

Ryzneuta for any use other than the specified, covered indications is considered not medically necessary. This includes, but is not limited to, use for PBPC collection and therapy, per the product labeling which explicitly states Ryzneuta is not indicated for mobilization of peripheral blood progenitor cells.

Providers requesting coverage must document that the proposed use falls within the policy’s approved indications; requests for off‑label or other unlisted uses will be denied as not medically necessary.

High febrile neutropenia risk threshold

High febrile neutropenia risk threshold>= 20% risk based on chemotherapy regimen

Intermediate risk context10%–20% risk — consider CSF if patient has additional risk factors per prescriber

Source guideline alignmentNCCN: prophylactic use recommended for >20% risk; consider for 10–20% with risk factors

Line of Therapy (informational)

Informational guidance on line of therapy:

Line of therapy: Policy does not specify a particular line of therapy; applies when the patient is receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia (e.g., regimens with >=20% risk) or when a prior neutropenic complication would compromise outcome if chemotherapy dose is reduced.

This is informational guidance only.

Chemotherapy regimen	Estimated febrile neutropenia risk	Notes / risk factors or qualification
Regimens associated with high risk based on NCCN guidance (examples include those with >20% incidence of febrile neutropenia)
≥ 20% (high)
Prophylactic CSF recommended for regimens with ≥20% FN risk. Policy approves Ryzneuta for patients receiving myelosuppressive anti-cancer medications with at least 20% FN risk based on the chemotherapy regimen.

Coding and HCPCS for Ryzneuta

Considered Medically Necessary HCPCS CodesHCPCSCovered

J9361

Injection, efbemalenograstim alfa-vuxw, 0.5 mg

HCPCS Codes (policy notes)mixed

J9361

Listed when criteria in the applicable policy statements are met (see policy for clinical criteria and dosing).

High febrile neutropenia risk threshold (quick reference)

Clinical quick reference — high risk>= 20% risk based on chemotherapy regimen

When intermediate risk applies10%–20% risk: require at least one patient-specific risk factor to justify prophylaxis

Age considerationExamples of risk factors include age > 65 years (receiving full chemotherapy dose intensity)

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior Authorization is required for benefit coverage of Ryzneuta. Approvals are recommended when the patient meets the documented Criteria and Dosing for the indicated use. All approvals are provided for the duration noted in the policy (when expressed in months, 1 month = 30 days). Ryzneuta must be prescribed by or in consultation with a physician who specializes in the condition being treated.

Prior authorization required for Ryzneuta
Approvals provided for durations listed in policy (1 month = 30 days)
Prescriber must be or consult a specialist (oncologist or hematologist)

Step Therapy

Preferred Product / Step Therapy Requirements

Employer plans: Ryzneuta requires a step trial of Rolvedon AND one pegfilgrastim product (documentation required). Pegfilgrastim examples: Neulasta, Fulphila, Fylnetra, Nyvepria, Udenyca, Stimufend, Ziextenzo. Individual and Family plans: Ryzneuta requires a trial of one pegfilgrastim product (documentation required).

Chemotherapy Regimens and Risk Stratification

Chemotherapy regimen	Estimated febrile neutropenia risk	Notes / risk factors or qualification
Regimens associated with intermediate risk (examples per NCCN: 10%–20% risk) where additional patient-specific risk factors increase FN risk
10%–20% (intermediate)
Consider CSF prophylaxis when patient has at least one prescriber-identified risk factor (e.g., age >65 receiving full dose intensity; prior chemo/radiation; persistent neutropenia; bone marrow tumor involvement; recent surgery/open wounds; bilirubin >2.0 mg/dL; CrCl <50 mL/min; poor performance status; HIV with low CD4). Policy requires documentation of at least one risk factor to approve Ryzneuta for regimens with <20% baseline risk.

Background on Ryzneuta and Indications

Ryzneuta is a granulocyte colony‑stimulating factor (G‑CSF) indicated to decrease the incidence of infection manifested by febrile neutropenia in adults receiving myelosuppressive anti‑cancer drugs associated with a clinically significant incidence of febrile neutropenia. The product labeling also specifies that safety and effectiveness in pediatric patients have not been established.

The prescribing information includes an explicit limitation of use: Ryzneuta is not indicated for mobilization of peripheral blood progenitor cells (PBPCs) for hematopoietic stem cell transplantation, which informs the policy’s exclusion of that indication.

Definitions

febrile neutropenia

DefinitionFebrile neutropenia: infection manifested by fever with neutropenia in patients receiving myelosuppressive anti-cancer drugs (Ryzneuta indicated to decrease incidence)

Limitation of useRyzneuta is not indicated for mobilization of peripheral blood progenitor cells (PBPCs) for hematopoietic stem cell transplantation

Pediatric noteSafety and effectiveness in pediatric patients have not been established

H-ARS (Hematopoietic Acute Radiation Syndrome)

DefinitionH-ARS (Hematopoietic Acute Radiation Syndrome): radiation-induced myelosuppression following a radiologic/nuclear incident affecting the hematopoietic system

Coverage contextPolicy allows approval for H-ARS for 1 month if patient is >= 18 years and medication prescribed by or in consultation with a physician experienced in treating acute radiation syndrome

Policy Revision History

2025-08-01policy_created

New policy created for Ryzneuta (IP0745) establishing coverage criteria, dosing, and prior authorization for cancer and H-ARS indications.

2025-12-01 to 2026-01-15criteria_and_dosing_update

Annual revision updated criteria language to 'Cancer in a Patient Receiving Myelosuppressive Chemotherapy', added risk‑stratified criteria and examples of risk factors, and specified dosing/approval durations for cancer and H‑ARS indications.

2026-01-15administrative_and_limit_additionsLatest