CurrentCentenePolicy CP PHAR.363

Enasidenib (Idhifa)

Defines medical necessity criteria, approval durations, and prescribing/administrative requirements for enasidenib (Idhifa) for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation, across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyEnasidenib (Idhifa)

Policy CodePolicy CP PHAR.363

Change TypeAnnual updates (NCCN alignment, generic requirement, approval duration revision)

Effective DateSep 5, 2017

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria, including IDH2 mutation test results.

POLICY UPDATE CHANGES

Added Idhifa combination with azacitidine per NCCN.

Removed age ≥ 60 requirement for use in non-relapsed/refractory disease per NCCN.

Requirement to use generic enasidenib if available.

Clarified use as single agent for all AML indications per NCCN (4Q2023).

Revised approval duration for Commercial line to 12 months or duration of request, whichever is less.

1FDA approved indication(s) (AML with IDH2 mutation)

100 mg/dayMaximum daily dose

30 daysMinimum duration on therapy prior to renewal

Commercial:12mInitial approval durations

6mInitial approval durations (Medicaid/HIM)

Coverage Summary

Coverage stance: covered_with_criteria. Scope: Defines medical necessity criteria, approval durations, and prescribing/administrative requirements for enasidenib (Idhifa) for treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation. FDA indication: Idhifa is indicated for the treatment of adult patients with relapsed or refractory AML with an IDH2 mutation. Boxed warning: differentiation syndrome is included and requires prompt corticosteroid therapy and hemodynamic monitoring if suspected. Approval durations: Commercial: 12 months (or duration of request, whichever is less); Medicaid/HIM: 6 months (initial) with renewal criteria specifying at least 30 days on therapy prior to continuation.

Thresholds

Age≥ 18 years

Maximum dose100 mg/day; 1 tablet/day

Minimum duration prior to renewal≥ 30 days on therapy

Initial approval duration (Commercial)12 months or duration of request, whichever is less

Initial approval duration (Medicaid/HIM)6 months

Minimum renewal duration30 days

Initial Therapy Criteria

Initial Approval Criteria

Idhifa is medically necessary when ALL of the following criteria are met:

ref”:

ref

Continuation Therapy Criteria

Continued Therapy (Renewal) Criteria

Continued therapy is authorized when ALL of the following are met:

ALL of the following

Member is currently receiving Idhifa via Centene benefit or documentation supports current use for AML and has received medication for at least 30 days.
Member is responding positively to therapy.
Member must use generic enasidenib, if available, unless contraindicated or clinically significant adverse effects are experienced.
Dose increase
- New dose limits if request is for dose increase

Other Diagnoses and Not Authorized Indications

Other Diagnoses / Indications

Coverage for other diagnoses/indications follows formulary/non-formulary or off-label policies:

ANY of the following

If drug is on formulary (Commercial, marketplace) or PDL (Medicaid): follow no-coverage criteria policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.33 (marketplace), CP PMN.255 (Medicaid).
If drug is NOT on formulary or PDL: follow non-formulary policy for the relevant line of business: CP.CPA.190 (commercial), HIM.PA.103 (marketplace), CP PMN.16 (Medicaid).
If diagnosis is non-FDA approved and not addressed in this policy: refer to off-label use policies CP.CPA.09 (commercial), HIM.PA.154 (marketplace), CP.PMN.53 (Medicaid) and evidence of coverage documents.

Diagnoses/Indications Not Authorized

Applicable Codes & Product Availability

Product availability (strengths)NDC

50 mg tablet	Enasidenib tablet strength available
100 mg tablet	Enasidenib tablet strength available

Provider Actions & Authorization Requirements

Prior Authorization

Prior authorization required

Requests must meet the policy's clinical criteria and will be reviewed; prescribed by or in consultation with an oncologist or hematologist is required.

Documentation Required

Support clinical criteria with documentation

Submit documentation such as office chart notes, laboratory results, or other clinical information supporting that the member meets all approval criteria, including IDH2 mutation test results.

Clinical Evidence & References

Evidence includes: Idhifa Prescribing Information (Dec 2023); National Comprehensive Cancer Network Acute Myeloid Leukemia Version 3.2024; and the NCCN Drugs & Biologics Compendium. The PI and NCCN sources note a boxed warning for differentiation syndrome. NCCN alignment is reflected in the policy updates, including addition of Idhifa in combination with azacitidine per the 4Q2024 review.

Background & Definitions

Background: Enasidenib (Idhifa) is an isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for adult patients with relapsed or refractory AML harboring an IDH2 mutation as detected by an FDA-approved test. The policy aligns coverage with the FDA indication and NCCN recommendations and includes the boxed warning for differentiation syndrome.

Definitions: AML — acute myeloid leukemia, a hematologic malignancy; NCCN — National Comprehensive Cancer Network, the guideline developer referenced for regimen recommendations; IDH2 — isocitrate dehydrogenase-2, the molecular target and required mutation for Idhifa eligibility.

Revision History

4Q 2024 (P&T Approval Date = 11.24)addedLatest

Consolidated NCCN Compendium scenarios; removed age ≥ 60 requirement for use in non-relapsed/refractory disease; added Idhifa (enasidenib) combination with azacitidine per NCCN (references reviewed and updated).

4Q 2023 (P&T Approval Date = 11.23; Date = 08.09.23)revised

Clarified use as a single agent for all AML indications per NCCN; references reviewed and updated.

4Q 2022 (P&T Approval Date = 11.22; Date = 08.02.22)revised

Policy Summary

PayerCentene

PolicyEnasidenib (Idhifa)

Policy CodePolicy CP PHAR.363

Change TypeAnnual updates (NCCN alignment, generic requirement, approval duration revision)

Effective DateSep 5, 2017

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria, including IDH2 mutation test results.

On This Page

New dose does not exceed 100 mg per day.

New dose does not exceed 1 tablet per day.

New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use; prescriber must submit supporting evidence.

Prescribed regimen must be FDA-approved or recommended by NCCN.

ALL of the following

Non-FDA approved indications are not authorized unless there is sufficient documentation of efficacy and safety per the referenced off-label use policies.

Billing Rule

Use generic enasidenib when available

Member must use generic enasidenib if a generic is available unless the generic is contraindicated or the member experiences clinically significant adverse effects.

Documentation Required

Dose increase justification

If requesting a dose increase beyond the prior dose, the prescriber must provide evidence that the new dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use.

Consolidated legacy WCG approval durations; in patients age ≥ 60 years, added that Idhifa must be used as a single agent and option to decline intensive therapy per NCCN; references reviewed and updated.

4Q 2021 (P&T Approval Date = 11.21; Date = 08.11.21)added

Added requirement to use generic enasidenib if available (unless contraindicated or significant adverse effects); added coverage for age ≥ 60 with specific NCCN scenarios; references reviewed and updated.

01.20.22 (affirmed 05.22)revised

Revised Commercial approval duration to 12 months or duration of request, whichever is less (change effective 01.20.22; P&T affirmed 05.22).

Effective 09.05.17 (policy inception)established

Policy aligns coverage with FDA indication for enasidenib (Idhifa) for adult patients with relapsed or refractory AML with an IDH2 mutation; boxed warning for differentiation syndrome and product availability includes 50 mg and 100 mg tablets.