Modifiedsierra health and lifePolicy N/A

Vyepti (eptinezumab) — coverage criteria for preventive treatment of migraine

Criteria and coverage position for use of intravenous eptinezumab (Vyepti) for prevention of migraine in members; includes initial and continuation authorization requirements, exclusions, coding, and supporting evidence. Affects providers requesting coverage for Vyepti infusion therapy.

Policy Summary

Payersierra health and life

PolicyVyepti (eptinezumab) — coverage criteria for preventive treatment of migraine

Policy CodePolicy N/A

Change TypeAdded ICD-10 codescontent updates

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization for up to 12 months after documenting migraine diagnosis per ICHD‑3, required migraine-day thresholds, prior trials/failures of specified preventives, and FDA‑concordant dosing.

SourceLink

POLICY UPDATE CHANGES

Added ICD-10 diagnosis codes G43.A0, G43.A1, G43.B0, G43.B1, G43.D0, and G43.D1.

Updated Background, Clinical Evidence, and References sections to reflect the most current information.

J3032HCPCS code

6ICD-10 codes added

12 moApproval period

≥8Migraine days (pathway)

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4–7Migraine days (alt)

Coverage Criteria for Vyepti (eptinezumab)

Initial Therapy

Covered when ALL of the following are met for initial therapy:

Initial therapy

Migraine frequency (one of the following)
- Pathway A: 4 to 7 migraine days per month; and one of the following: less than 15 headache days per month; or provider attests this is the member's predominant headache diagnosis (i.e., primary driver of headaches is not a different, non-migrainous condition).
- Pathway B: >= 8 migraine days per month.
Prior preventive therapy
- Oral/other prophylactics (select two): Amitriptyline or nortriptyline; one of the following beta-blockers: atenolol, metoprolol, nadolol, propranolol, or timolol; candesartan; divalproex sodium; onabotulinumtoxinA (trial of at least 2 quarterly injections/6 months); topiramate; duloxetine or venlafaxine.
Prior CGRP therapies (when specified): Trial and failure (after a trial of at least three months), contraindication, or intolerance to two of the following CGRP therapies (for certain reviews/Medicare reviews): Aimovig (erenumab), Emgality (galcanezumab 120 mg), Nurtec ODT (rimegepant), Qulipta (atogepant).
Concomitant biologic CGRP therapy: Medication will not be used in combination with another biologic CGRP antagonist or inhibitor used for the preventive treatment of migraines (e.g., Aimovig, Emgality, Nurtec ODT, Qulipta).
Dosing and authorization: Dosing is in accordance with FDA approved labeling; authorization will be issued for no more than 12 months.

Continuation Therapy

Covered for continuation when ALL of the following are met:

Continuation therapy: Patient has experienced a positive response to therapy demonstrated by a reduction in headache frequency and/or intensity; and medication will not be used in combination with another biologic CGRP antagonist or inhibitor used for the preventive treatment of migraines (e.g., Aimovig, Emgality, Nurtec ODT, Qulipta); and dosing is in accordance with FDA approved labeling; and reauthorization will be issued for no more than 12 months.

Continuation requires objective clinical improvement and maintains prohibitions on combination CGRP biologics and FDA-concordant dosing.

Coverage context and qualifying statements

Clinical guidance and FDA indication context

Clinical guidance: Professional society guidance: ACP suggests use of CGRP-targeting therapies after failure/intolerance to specified traditional preventives (conditional recommendation); AHS states CGRP-targeting therapies are a first-line option for migraine prevention.

Summarizes ACP conditional recommendation and AHS position supporting first-line use.

FDA indication for Vyepti: Vyepti (eptinezumab) is indicated for preventive treatment of migraine in adults; efficacy was evaluated in randomized placebo-controlled trials for episodic and chronic migraine.

Recommended dosage per FDA: 100 mg IV every 3 months; some patients may benefit from 300 mg IV every 3 months.

Vyepti (eptinezumab) is unproven and not medically necessary for the treatment of acute migraine attacks and for episodic cluster headache.

The FDA information in this policy is provided for informational purposes only; FDA approval alone is not a basis for coverage under this policy.

Use of Vyepti for an acute attack of migraine or for episodic cluster headache is considered unproven and is not covered as medically necessary.

This policy is intended to assist interpretation of benefit plans and is provided for informational purposes only. Coverage determinations depend on the member-specific benefit plan; in the event of a conflict, the member-specific benefit plan document governs. The policy does not constitute medical advice.

Coding — HCPCS, ICD-10, Dosing

Applicable HCPCS CodesHCPCSCovered

J3032

Injection, eptinezumab-jjmr, 1 mg.

Applicable Diagnosis CodesICD-10

G43.001	Migraine without aura, not intractable, with status migrainosus.
G43.009	Migraine without aura, not intractable, without status migrainosus.
G43.011	Migraine without aura, intractable, with status migrainosus.
G43.019	Migraine without aura, intractable, without status migrainosus.
G43.101	Migraine with aura, not intractable, with status migrainosus.
G43.109	Migraine with aura, not intractable, without status migrainosus.
G43.111	Migraine with aura, intractable, with status migrainosus.
G43.119	Migraine with aura, intractable, without status migrainosus.
G43.401	Hemiplegic migraine, not intractable, with status migrainosus.
G43.409	Hemiplegic migraine, not intractable, without status migrainosus.

1–10 of 48

1/5

Added ICD-10 diagnosis codesICD-10Covered

G43.A0	ICD-10 diagnosis code added per policy history
G43.A1	ICD-10 diagnosis code added per policy history
G43.B0	ICD-10 diagnosis code added per policy history
G43.B1	ICD-10 diagnosis code added per policy history
G43.D0	ICD-10 diagnosis code added per policy history
G43.D1	ICD-10 diagnosis code added per policy history

Drug dosing (informational)mixed

not provided

Drug administration — Vyepti 100 mg and 300 mg IV every 3 months (per prescribing information).

inv-12: Monthly migraine days — qualifying thresholds (4–7 days or ≥8 days pathways)

Pathway A — lower-frequency4–7 migraine days per month AND either <15 headache days per month OR provider attests migraine is the predominant headache diagnosis

Pathway B — higher-frequency>= 8 migraine days per month

Documentation requirementBaseline migraine days per month must be documented to support pathway selection

inv-13: Vyepti dosing interval — 100 mg q3 months; some patients may benefit from 300 mg q3 months

Recommended dosing interval (standard)100 mg IV every 3 months

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Vyepti (eptinezumab) for preventive treatment of migraine. Authorization may be issued for up to 12 months when initial criteria are met. Verify the member's specific benefit plan and any applicable federal or state mandates before submitting a request. In the event of a conflict, the member-specific benefit plan document governs.

Authorization duration: up to 12 months for initial approval and reauthorization
Verify member-specific plan document; member plan controls if conflicts exist
Check for Medicare Advantage-specific requirements when applicable

Denial Risk

Unproven / Not Medically Necessary Indications

Requests for Vyepti for acute treatment of a migraine attack or for episodic cluster headache are considered unproven and not medically necessary and should not be authorized.

Background and Clinical Rationale

Background: Eptinezumab (Vyepti) is a humanized IgG1 monoclonal antibody that binds the calcitonin gene-related peptide (CGRP) ligand, blocking its interaction with the receptor. Phase 3 evidence supporting its preventive use in migraine comes from the PROMISE program: PROMISE 1 (episodic migraine) and PROMISE 2 (chronic migraine), randomized, double-blind, placebo-controlled trials that demonstrated reductions in monthly migraine days versus placebo. Per the FDA prescribing information, Vyepti is indicated for preventive treatment of migraine in adults with a recommended dose of 100 mg IV every 3 months and some patients may benefit from 300 mg IV every 3 months.

Definitions and Key Terms

inv-23: Vyepti (eptinezumab) — humanized IgG1 monoclonal antibody that binds CGRP ligand

Molecule classHumanized immunoglobulin G1 (IgG1) monoclonal antibody

TargetBinds the calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor

Brand and genericVyepti (eptinezumab)

inv-24: Key clinical trials — PROMISE 1 & 2 Phase 3 trials cited as clinical evidence

PROMISE 1Phase 3 randomized, double-blind, placebo-controlled trial for episodic migraine (eptinezumab 300 mg, 100 mg, 30 mg vs placebo); showed significant reductions in monthly migraine days

PROMISE 2Phase 3 randomized, double-blind, placebo-controlled trial for chronic migraine (eptinezumab 300 mg or 100 mg vs placebo); showed significant reductions in monthly migraine days and responder rates

Policy Revision History

2025-09-01codes_addedLatest

Policy history notes addition of six ICD-10 diagnosis codes (G43.A0, G43.A1, G43.B0, G43.B1, G43.D0, G43.D1) to the Applicable Codes list.

Policy Summary

Payersierra health and life

PolicyVyepti (eptinezumab) — coverage criteria for preventive treatment of migraine

Policy CodePolicy N/A

Change TypeAdded ICD-10 codescontent updates

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

Alternate dosing for some patients

300 mg IV every 3 months (may benefit some patients)

Dosing documentationAuthorization requires dosing in accordance with FDA labeling

Not medically necessary: acute attack of migraine
Not medically necessary: episodic cluster headache

Note

Coverage May Vary by Member-Specific Benefit Plan

Coverage and medical necessity criteria may vary by member-specific benefit plan. Always review the member's plan document and any applicable federal or state mandates. In the absence of a Medicare NCD or LCD for eptinezumab, Medicare Advantage organizations may apply their own coverage determinations using objective evidence-based rationale; refer to Medicare Part B Step Therapy Programs for preferred therapy criteria when applicable.

Medicare: no NCD or LCD exists for eptinezumab; refer to CMS and MAO guidance
MA plans may apply Medicare Part B Step Therapy Programs for preferred therapy criteria
Member-specific benefit plan governs if conflicts arise

Step Therapy

Step Therapy / Prior Trials Required

Step therapy/prior trials are required before initial authorization. For non-Medicare members, trial and failure (after trial of at least two months), contraindication, or intolerance to two prophylactic therapies from the listed classes is required. Additionally, trial and failure (after trial of at least three months), contraindication, or intolerance to two other CGRP-targeted preventive therapies is required (for Medicare reviews, see Medicare-specific note).

Trial/failure (≥2 months), contraindication, or intolerance to two prophylactic therapies from: tricyclic antidepressant (amitriptyline or nortriptyline); beta-blocker (atenolol, metoprolol, nadolol, propranolol, timolol); candesartan; divalproex sodium; onabotulinumtoxinA (≥2 quarterly injections/6 months); topiramate; SNRI (duloxetine or venlafaxine).
Trial/failure (≥3 months), contraindication, or intolerance to two of the listed CGRP-targeted therapies (e.g., Aimovig, Emgality 120 mg, Nurtec ODT, Qulipta).
Medication must not be used in combination with another biologic CGRP antagonist/inhibitor for migraine prevention.

Note

Medicare Advantage Step Therapy Note

For Medicare Advantage members, refer to the Medicare Part B Step Therapy Programs for preferred therapy criteria. Medicare does not have a National Coverage Determination (NCD) or Local Coverage Determinations (LCDs) for eptinezumab; MA organizations may establish their own coverage rules using evidence-based rationale. Also ensure Part B coverage rules (drugs furnished "incident to" a physician service) are considered where applicable.

Medicare: no NCD/LCD for Vyepti (eptinezumab); LCDs/LCAs do not exist
Refer to Medicare Part B Step Therapy Programs for preferred therapy criteria for MA members
Consider Medicare Benefit Policy Manual, Chapter 15, §50 when assessing Part B coverage

Study design commonalityBoth trials were IV infusions administered once every 12 weeks and demonstrated early onset of benefit and acceptable safety vs placebo

inv-25: Vyepti (eptinezumab) — CGRP antagonist indicated for preventive treatment of migraine; recommended dosage noted

IndicationCGRP antagonist indicated for preventive treatment of migraine in adults

Recommended dosage100 mg administered by IV infusion every 3 months; some patients may benefit from 300 mg IV every 3 months

Evidence baseEfficacy evaluated in randomized placebo-controlled studies for episodic and chronic migraine

inv-26: CGRP-targeting therapies — definition and context for migraine-specific therapies

DefinitionTherapies that target the calcitonin gene-related peptide (CGRP) pathway

Clinical contextConsidered 'migraine-specific' with evidence supporting efficacy, tolerability, and use across episodic and chronic migraine

Guideline positionsACP suggests use after failure/intolerance to certain traditional preventives (conditional); AHS states CGRP-targeting therapies are a first-line option