CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Onureg (oral azacitidine) — coverage criteria for AML maintenance

Defines accepted indications, exclusions, coding, and documentation requirements for Onureg (oral azacitidine) for members, including FDA-approved and accepted off-label uses; applies to providers submitting medication requests to Evolent for Neighborhood Health Plan of Rhode Island lines of business.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyOnureg (oral azacitidine) — coverage criteria for AML maintenance

Policy CodePolicy N/A

Change TypeUpdated exclusions and template migration

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization documenting AML maintenance indication and that dosing and tablet limits are not exceeded.

SourceLink

POLICY UPDATE CHANGES

Updated exclusion criteria for Onureg usage.

Converted to new Evolent guideline template and replaced prior UM ONC_1416 Onureg guideline.

Updated references and sources supporting policy (QUAZAR trial, prescribing info, compendia).

300 mgsingle dose maximum of Onureg

14maximum monthly tablet limit

J8999billing code

Commercial/Medicaidapplicable lines

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Coverage Criteria for Onureg (oral azacitidine)

AML maintenance — covered

Covered when ALL of the following are met:

AML maintenance indication: Member has acute myeloid leukemia in first complete remission following induction therapy

based on FDA/QUAZAR evidence

Consolidation unsuitability: Member is unable to receive or is considered clinically unsuitable to receive 3 or more cycles of consolidation therapy after induction and achievement of complete remission (e.g., high‑dose cytarabine [HiDAC])

policy criterion

Supporting evidence: Use is supported by FDA labeling, CMS‑recognized compendia, NCCN or ASCO guidelines, or peer‑reviewed literature meeting CMS criteria

documentation requirement

Onureg (oral azacitidine) is not appropriate as a substitution for intravenous hypomethylating agents used to treat myelodysplastic syndromes. Specifically, use as a substitute for IV Vidaza (azacitidine) or Dacogen (decitabine) for MDS is excluded.

Treatment requests will be denied when the member has completed 3 or more cycles of cytarabine-based consolidation therapy (e.g., High‑dose Ara‑C ×3 or more cycles) after achieving complete remission.

Other exclusion triggers include disease progression while receiving Onureg or another hypomethylating agent, and dosing that exceeds the policy limits (see coding thresholds).

Onureg is considered not medically necessary for investigational or off‑label indications that lack sufficient supporting evidence as defined by CMS‑recognized compendia or acceptable peer‑reviewed literature.

The policy defines insufficient evidence by assessing whether the clinical population and regimen are adequately represented in published data, whether outcomes are clinically meaningful (e.g., ASCO standards such as Hazard Ratio <0.80 or survival benefit ≥3 months), and by the quality of study design. Case reports, meeting abstracts without full peer‑reviewed publication, and uncontrolled anecdotal reports are generally not sufficient to support coverage.

Covered Regimens and Indications

Regimen	Indication	Coverage status
Onureg (oral azacitidine) single-agent
Maintenance therapy in acute myeloid leukemia (AML) in first complete remission following induction when the member is unable to receive or is considered clinically unsuitable to receive 3 or more cycles of consolidation therapy (e.g., HiDAC).
Covered with criteria

Line of Therapy

first-line

Line of therapy: Used as maintenance therapy in first complete remission after induction when consolidation (≥3 cycles) is not possible or is considered clinically unsuitable

first‑line maintenance after induction

Billing and Coding

Drug HCPCS CodeHCPCSCovered

J8999

azacitidine oral

inv-05: Single dose limit — 300 mg

Single dose maximumOnureg (azacitidine oral) single dose limit of 300 mg

Policy consequenceDosing requests that exceed the 300 mg single dose limit are grounds for exclusion/denial

Source guidanceLimit stated in Exclusion Criteria as dosing exceeds single dose limit of Onureg 300 mg

inv-06: Maximum tablets per month — 14 (300 mg) or 14 (200 mg) tablets/month

Monthly tablet maximum (300 mg formulation)Maximum of 14 tablets per month (300 mg formulation)

Monthly tablet maximum (200 mg formulation)Maximum of 14 tablets per month (200 mg formulation)

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Onureg requests. Documentation submitted with the prior authorization must support the indication (for example: AML maintenance therapy in first complete remission when the member is unable or clinically unsuitable for consolidation therapy) and include relevant clinical notes, prior treatment history, and citations to FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or peer-reviewed literature.

Prior authorization required for Onureg (azacitidine oral).
Include documentation of indication and supporting evidence (FDA label, CMS compendia, NCCN/ASCO, or peer-reviewed literature).

Step Therapy

Therapy Positioning / Step

Onureg is positioned as a single‑agent maintenance therapy for Acute Myeloid Leukemia (AML) in members who are in first complete remission following induction therapy and who are unable to receive or are considered clinically unsuitable to receive 3 or more cycles of consolidation therapy (e.g., high‑dose cytarabine). It is not intended as a substitute for standard consolidation regimens.

Definitions

inv-12: Maintenance therapy (Onureg) — definition for maintenance therapy use

DefinitionMaintenance therapy: single‑agent oral azacitidine (Onureg) used to prolong remission in adults with AML in first complete remission after induction when the member is unable or considered clinically unsuitable to receive 3 or more cycles of cytarabine‑based consolidation (e.g., HiDAC)

Indication contextIntended for patients in first complete remission following induction therapy

Consolidation requirementUsed when consolidation with 3+ cycles is not feasible or clinically appropriate

Background

Onureg (oral azacitidine) is indicated as maintenance therapy for adults with acute myeloid leukemia who are in first complete remission after induction and who are unable or considered clinically unsuitable to receive three or more cycles of cytarabine‑based consolidation.

Evidence supporting this indication includes randomized trial data and the product prescribing information; use must adhere to policy limits and exclusions (for example, dosing thresholds and prohibitions on substitution for IV hypomethylating agents).

Revision History and Policy Changes

April 2025operational/clinical revisionLatest

Converted to new Evolent guideline template, replaced prior UM ONC_1416 Onureg guideline, updated exclusion criteria, and updated references.

April 2024administrative update

Updated NCH verbiage to Evolent.