CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Idhifa (enasidenib) coverage for IDH2-mutated AML

Defines accepted indications, coverage criteria, exclusions, and coding for enasidenib (Idhifa) for members of Neighborhood Health Plan of Rhode Island processed by Evolent; applies to medication requests from network ordering providers.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyIdhifa (enasidenib) coverage for IDH2-mutated AML

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization through Evolent and document confirmed IDH-2 mutation positivity with an FDA-approved test; ensure dosing and monthly tablet limits are within policy limits.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

100single dose limit (mg)

30max tablets/month

J8999billing code

6lines of business

Coverage Criteria for Idhifa (enasidenib)

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inv-02: Continuation Therapy

Continuation requests may be exempt from re-review when ALL of the following are met

Continuation criteria: Member has not experienced disease progression on the requested medication; medication was used within the last year without a lapse of more than 30 days of having an active authorization; no additional medications are being added to the continuation request

If met, continuation requests are exempt from this Evolent policy

Coverage for Idhifa (enasidenib) is subject to specific limitations and conditions. Therapy will be denied if the medication is being used after documented disease progression on Idhifa, if there is no documentation of IDH‑2 mutation positivity, or if dosing exceeds the single‑dose limit of 100 mg. Treatment that would result in dispensing more than the maximum monthly tablet limit — stated as 30 (50 mg) tablets/month or 30 (100 mg) tablets/month — is not allowed. Requests that propose investigational or off‑label uses are evaluated against the evidentiary standards described below and are excluded when the indication lacks sufficient evidence or broad acceptance by the medical community.

Use of Idhifa (enasidenib) for investigational or off‑label indications that are not supported by authoritative evidence is considered not medically necessary. Sufficient evidence is defined by whether the population and regimen are adequately represented in the published literature, whether study outcomes are clinically meaningful (for example, ASCO‑recommended thresholds such as hazard ratio < 0.80 or survival benefit of at least 3 months for OS/PFS), and whether study design is appropriate to the question. Case reports and meeting abstracts without full peer‑reviewed publication generally do not meet the standard; non‑randomized trials with substantial subject numbers may be considered supportive in some circumstances.

Regimen	Indication / Line of therapy	Coverage status
Single-agent enasidenib (Idhifa)
Relapsed or refractory IDH2‑mutated acute myeloid leukemia (AML) OR single‑agent use in a member not suitable for standard induction/consolidation chemotherapy
Covered with criteria

Provider Requirements and Authorization

Prior Authorization

Prior Authorization Required

Prior authorization required through Evolent for all Idhifa (enasidenib) medication requests. Continuation requests may be exempt when the member has not experienced disease progression on the requested medication, the medication was used within the last year without a lapse greater than 30 days of an active authorization, and no additional medications are being added to the continuation request.

All initial and reauthorization requests must be submitted to Evolent.
Continuation exemptions apply only when conditions above are met.

Step Therapy

Step therapy: Not applicable / No step therapy required prior to authorization for Idhifa (enasidenib).

There is no documented requirement to trial another agent before Idhifa is authorized.
Providers should still include prior treatment history in the request to support medical necessity.

Documentation Required

Required Documentation

Documentation must demonstrate a confirmed diagnosis of IDH-2 mutation positive AML and that dosing and quantity requests fall within stated limits.

Confirmatory test: any FDA-approved test documenting IDH-2 mutation positivity must be provided.
Dosing limits: single dose must not exceed 100 mg; monthly quantity must not exceed 30 tablets (50 mg) or 30 tablets (100 mg) as applicable.
Include clinical rationale if member is not a candidate for standard induction/consolidation chemotherapy.

Denial Risk

Triggers for Denial

Denial may be issued if exclusion criteria are met or documentation is insufficient.

Lack of documentation of IDH-2 mutation positivity.
Use after documented disease progression on prior Idhifa therapy.
Dosing exceeds single-dose limit of 100 mg or monthly quantity limits.
Investigational or off-label use without sufficient supporting evidence from FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature.

Key Definitions

IDH-2 mutation positive AML — definition and confirmatory testing requirement

DefinitionAcute myeloid leukemia (AML) in which the tumor harbors an IDH-2 (IDH2) gene mutation confirmed with any FDA‑approved test

Indications for useIdhifa (enasidenib) may be used as a single agent for relapsed or refractory disease OR as a single agent in a member not suitable for standard induction/consolidation chemotherapy

Documentation requirementCoverage requires documentation of confirmed IDH-2 mutation status (confirmed with any FDA‑approved test); lack of this documentation is a trigger for denial

IDH2 — Positive mutation confirmed with any FDA-approved test

Mutation test requirementPositive IDH2 mutation must be confirmed with any FDA‑approved test

Acceptable evidenceConfirmation by any FDA‑approved diagnostic test per policy language; documentation must be provided with the request

PurposeIDH2 positivity is required to qualify for Idhifa (enasidenib) therapy as specified in coverage criteria

Line of Therapy Specification

inv-13: second-line

Line of therapy: Use as single agent for relapsed or refractory disease OR as single agent in a member not suitable for standard induction/consolidation chemotherapy

Specifies relapsed/refractory or unsuitable-for-intense-chemotherapy contexts

Background on Enasidenib (Idhifa)

Enasidenib (Idhifa) is indicated for treatment of patients with relapsed or refractory acute myeloid leukemia (AML) harboring an IDH2 mutation and may be used as a single agent in relapsed/refractory disease or in patients who are not suitable for standard induction/consolidation chemotherapy. Coverage is limited to members with a confirmed IDH‑2 mutation positive AML (confirmed with any FDA‑approved test) and is contingent on meeting the dosing and documentation requirements noted in this policy.