CurrentCentenePolicy CP.PHAR.363

Enasidenib (Idhifa) Coverage Criteria

Medical necessity and prior authorization criteria for enasidenib (Idhifa) for treatment of adult patients with acute myeloid leukemia (AML) with an IDH2 mutation, applicable to Centene-affiliated health plans and providers submitting requests.

Policy Summary

PayerCentene

PolicyEnasidenib (Idhifa) Coverage Criteria

Policy CodePolicy CP.PHAR.363

Change TypeNo material change

Effective DateSep 5, 2017

Next Review Date

Key ActionProvider must submit documentation (office notes, lab results, or other clinical information) supporting that member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

100 mg/daymaximum recommended dose

Age ≥ 18minimum age for coverage

12 monthsapproval duration

IDH2 mutationmandatory biomarker

Coverage Criteria for Enasidenib (Idhifa)

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Initial approval - AML: 1) Diagnosis of acute myeloid leukemia (AML); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Prescribed as either: a) single-agent therapy, or b) in combination with azacitidine; 5) Member is either: a) relapsed or refractory, or b) not a suitable candidate for or declines intensive induction chemotherapy; 6) Presence of an IDH2 mutation; 7) Member must use generic enasidenib if available unless contraindicated or clinically significant adverse effects are experienced; 8) Request meets one of the following: a) dose does not exceed both i) 100 mg per day and ii) 1 tablet per day, or b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose ≤ 100 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN; approval duration: 12 months

inv cu-02: Continuation Therapy

Continued coverage when ALL of the following are met:

Continuation therapy - AML: 1) Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Idhifa for AML and has received this medication for at least 30 days; 2) Member is responding positively to therapy; 3) Member must use generic enasidenib if available unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, request meets one of the following: a) new dose does not exceed both i) 100 mg per day and ii) 1 tablet per day, or b) new dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose ≤ 100 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN; approval duration: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less

Non-FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the referenced off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or other applicable evidence of coverage documents.

Initial Therapy — AML

inv cu-15: Initial Therapy - AML

Initial approval criteria for Idhifa in AML

Initial: Diagnosis of AML; prescribed by or in consultation with an oncologist or hematologist; age ≥ 18 years; prescribed as single-agent therapy or in combination with azacitidine; disease is relapsed or refractory or member is not a suitable candidate for or declines intensive induction chemotherapy; presence of an IDH2 mutation; member must use generic enasidenib if available unless contraindicated or clinically significant adverse effects are experienced; dosing does not exceed 100 mg/day and 1 tablet/day OR dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose ≤ 100 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN; approval duration: 12 months

Continuation Criteria

inv cu-16: Continuation

Criteria for continued Idhifa coverage

Continuation: Member currently receiving medication via Centene benefit or has received Idhifa for ≥ 30 days; member is responding positively to therapy; member must use generic enasidenib if available unless contraindicated or clinically significant adverse effects are experienced; if request is for a dose increase, new dose must not exceed 100 mg/day and 1 tablet/day OR be supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence).dose ≤ 100 mg/day

Prescribed regimen must be FDA-approved or recommended by NCCN; approval duration: Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less

Coding and Product Information

Covered diagnosis (informational)ICD-10

ICD-10 unspecified

Acute myeloid leukemia with IDH2 mutation (documented requirement in policy)

Product availability / NDCNDC

NDC not listed

Tablets: 50 mg, 100 mg (product availability)

Maximum daily dose — 100 mg per day

Maximum daily dose100 mg per day (do not exceed 1 tablet per day unless supported by guidelines or literature)

Dosing regimen for AML100 mg PO once daily

Dose exceptionsHigher doses permitted only if supported by practice guidelines or peer‑reviewed literature with prescriber submission of evidence

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization required — Prior authorization is required. Provider must document that all approval criteria for Idhifa (diagnosis of AML, presence of IDH2 mutation, prescriber specialty, age, dosing limits or supporting literature, etc.) are met.

Prescriber specialty: oncologist or hematologist required (or consult).
Age: ≥ 18 years.
Diagnosis: Acute Myeloid Leukemia with documented IDH2 mutation.
Dosing: ≤ 100 mg/day and 1 tablet/day unless supported by guidelines or literature.

Billing Rule

Generic Required When Available

Generic required when available — Member must use generic enasidenib (enasidenib) if available unless there is a documented contraindication or the member experienced clinically significant adverse effects.

Documentation Required

Required Supporting Documentation

Required supporting documentation — Provider must submit documentation (office chart notes, laboratory results, molecular testing confirming IDH2 mutation, treatment history, and any supporting literature when dosing outside usual limits) that demonstrates the member meets all approval criteria.

Include molecular testing that documents IDH2 mutation.
Include prior therapy history to support relapsed/refractory status or unsuitability for intensive induction chemotherapy.
Include rationale and citations if dose exceeds standard limits.

Denial Risk

Insufficient Documentation or Non‑Covered Indication

Insufficient documentation or non-covered indication — Requests that lack documentation demonstrating the member meets the approval criteria, or requests for non‑FDA‑approved indications not supported by sufficient off‑label evidence per applicable off‑label use policies, will not be authorized.

Non‑FDA indications require sufficient documentation of efficacy and safety per CP.CPA.09 (commercial), HIM.PA.154 (marketplace), or CP.PMN.53 (Medicaid).
Incomplete charting, missing molecular testing, or absent specialist involvement may result in denial.

Step	Requirement
1	Member must use generic enasidenib if available unless contraindicated or clinically significant adverse effects are experienced.

Background

Enasidenib (Idhifa) is an isocitrate dehydrogenase‑2 (IDH2) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation. The drug carries a boxed warning for differentiation syndrome; suspected cases require prompt treatment with corticosteroids and appropriate hemodynamic monitoring.

Definitions

Enasidenib (Idhifa) — IDH2 inhibitor definition

Drug classIDH2 inhibitor (isositrate dehydrogenase-2 inhibitor)

Approved indication (informational)Treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation

Common drug namesIdhifa; enasidenib

Differentiation syndrome — definition and management note

DefinitionDifferentiation syndrome: a boxed warning adverse event associated with enasidenib; requires prompt recognition and management

Immediate managementIf suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution

Clinical noteDifferentiation syndrome is a potentially serious, treatment‑emergent complication listed as a boxed warning in the product information