ModifiedNeighborhood Health Plan of Rhode IslandPolicy N/A

Onureg (azacitidine oral) coverage and authorization criteria

Defines accepted indications, continuation and exclusion criteria, contraindications, coding, and documentation standards for coverage and authorization of Onureg (oral azacitidine) across multiple lines of business. Specifies evidentiary sources required for non-FDA uses and continuation exemptions.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyOnureg (azacitidine oral) coverage and authorization criteria

Policy CodePolicy N/A

Change TypeConverted to new Evolent guideline template; updated exclusion criteria and references

Effective Date

Next Review Date

Key ActionEvolent must process all medication requests and ensure use is supported by FDA labeling, CMS-approved compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature per CMS Chapter 15 standards.

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and replaced prior UM ONC_1416 Onureg (azacitidine oral).

Updated NCH verbiage to Evolent (April 2024).

1Covered Indication (AML maintenance in CR unable to receive ≥3 consolidation cycles)

6Explicit Exclusion Criteria Count

1Primary HCPCS code listed

Coverage Summary

Coverage stance: covered_with_criteria for Onureg (oral azacitidine). This policy defines accepted indications, continuation and exclusion criteria, contraindications, coding, and documentation standards for coverage and authorization of Onureg across multiple lines of business. Evolent is responsible for processing medication requests and determining approvability and reimbursement; use must be supported by FDA labeling, CMS-approved compendia, NCCN or ASCO guidelines, or acceptable peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 standards.

Accepted indication (primary): Onureg may be used as a single agent maintenance therapy in members with Acute Myeloid Leukemia (AML) in first complete remission (CR) following induction therapy who are unable to receive or are considered clinically unsuitable to receive 3 or more cycles of consolidation therapy after induction and achievement of CR.

Continuation criteria and exemptions: Continuation requests for a previously non-approvable medication are exempt from non-approvable status when all of the following are met: member has not experienced disease progression on the requested medication; the medication was used within the last year without a lapse of more than 30 days from an active authorization; and no additional medications are being added to the continuation request.

Exclusion criteria and not medically necessary uses: Use is not approved when any of the following apply: substitution of Onureg for intravenous Vidaza (azacitidine) or Dacogen (decitabine) for MDS; use after completion of 3 or more cycles of cytarabine-based consolidation; disease progression while taking Onureg or another hypomethylating agent; dosing exceeding the single dose limit of 300 mg; treatment exceeding the maximum monthly tablet limit of 14 tablets/month (14 x 300 mg or 14 x 200 mg); or investigational/off-label indications lacking sufficient evidence or general acceptance.

Contraindications: History of severe hypersensitivity to azacitidine or any component of the product.

Coding and reporting: Report supply and billing using J8999 (azacitidine oral).

Provider Actions & Requirements

Prior Authorization

Authorization requirement and evidentiary support

Evolent must process all medication requests for Onureg (azacitidine oral). Authorization is required and use must be supported by one or more of the following evidentiary sources: FDA-approved product labeling, CMS‑approved compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature that meets the CMS Medicare Benefit Policy Manual Chapter 15 standards. Report azacitidine oral using HCPCS code J8999.

Required evidence sources: FDA labeling; CMS‑recognized compendia; NCCN or ASCO guidelines; peer‑reviewed literature meeting CMS Chapter 15
HCPCS code for billing/identification: J8999

Prior Authorization

Continuation request exemption criteria

Continuation (renewal) requests for a previously non‑approvable medication are exempt from the non‑approvable policy when all of the following are documented: no disease progression on the requested medication; the medication was used within the past year with no lapse of more than 30 days of having an active authorization; and no additional medication(s) are being added to the continuation request.

No disease progression on the requested medication
Used within last year with ≤30‑day lapse from active authorization
No additional medications added to the request

Documentation Required

Clinical suitability for avoiding consolidation therapy

Document clinical suitability that the member is unable or clinically unsuitable to receive three or more cycles of consolidation therapy after induction and achievement of complete remission to support use of Onureg as maintenance in AML. Include HCPCS code J8999 on requests.

Statement that member cannot receive or is clinically unsuitable for ≥3 cycles of consolidation therapy after induction and CR
Reference to maintenance use in AML first remission
Include code J8999

Denial Risk

Exclusion / investigational denials

Requests will be non‑approvable if any of the following apply: substitution of Onureg for IV azacitidine (Vidaza) or decitabine (Dacogen) for MDS; member has completed three or more cycles of cytarabine‑based consolidation after achieving CR; disease progression while taking Onureg or another hypomethylating agent; dosing exceeds single dose limit of 300 mg or monthly tablet limits (maximum 14 tablets/month of the listed strengths); or off‑label use lacks sufficient evidence as defined by required sources and CMS Chapter 15 standards.

Substitution for IV Vidaza (azacitidine) or Dacogen (decitabine) for MDS
Completed ≥3 cycles of cytarabine‑based consolidation therapy after CR
Disease progression on Onureg or another hypomethylating agent
Single dose limit exceeded: 300 mg
Monthly tablet limits exceeded: maximum 14 tablets/month (300 mg or 200 mg strengths)
Off‑label indications lacking evidence from FDA labeling, CMS compendia, NCCN/ASCO, or peer‑reviewed literature meeting CMS Chapter 15

Billing Rule

Code reporting

Supply and bill oral azacitidine using HCPCS code J8999.

Report and bill azacitidine oral with J8999

Clinical Evidence & References

Onureg PIOnureg prescribing information, Bristol-Myers Squibb Company, 2022 (labeling and dosing limits)

Dose limitsSingle dose limit 300 mg; monthly tablet limit maximum 14 tablets/month (300 mg or 200 mg)

Key evidence supporting coverage includes the QUAZAR AML-001 randomized, placebo-controlled phase 3 trial demonstrating oral azacitidine maintenance in AML first remission (published NEJM and Am J Hematol updates).

Additional evidentiary sources referenced include the Onureg prescribing information (Bristol-Myers Squibb, 2022) and recognized standards such as CMS compendia, NCCN, and ASCO guidelines, which are accepted per the policy's evidentiary requirements.

Definitions

Continuation request exemption: Criteria under which continuation of a previously non-approvable medication may still be processed — no disease progression on the requested medication, prior use within the last year with a lapse of ≤ 30 days from an active authorization, and no additional medications added to the continuation request.

Sufficient evidence: Evidence supported by FDA labeling, CMS-approved compendia, NCCN/ASCO guidelines, or peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 criteria; assessment includes whether patient and cancer characteristics and the administered therapy regimen are represented in the published evidence, whether reported outcomes are clinically meaningful (ASCO guidance, e.g., hazard ratio < 0.80 and survival benefit for OS/PFS of at least 3 months), and whether the experimental design is appropriate. Non-randomized trials with significant subject numbers may be supportive; case reports and abstracts without full peer-reviewed articles are generally insufficient.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyOnureg (azacitidine oral) coverage and authorization criteria

Policy CodePolicy N/A

Change TypeConverted to new Evolent guideline template; updated exclusion criteria and references

Effective Date

Next Review Date

On This Page

OpenPayer

Onureg (azacitidine oral) coverage and authorization criteria

Coverage Summary

Continuation Therapy Criteria

Contraindications & Warnings

Exclusion Criteria / Not Medically Necessary

Applicable Codes

Provider Actions & Requirements

Clinical Evidence & References

Definitions

Background

Revision History