ModifiedColorado Rocky Mountain Health PlansPolicy 2025D0090M

Vyepti® (Eptinezumab-Jjmr) – Commercial Medical Benefit Drug Policyopen_in_new

Defines medical necessity criteria, continuation/reauthorization criteria, exclusions, applicable procedure and diagnosis codes, and supporting clinical evidence for intravenous eptinezumab (Vyepti) for preventive treatment of migraine in adults.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyVyepti® (Eptinezumab-Jjmr) – Commercial Medical Benefit Drug Policyopen_in_new

Policy CodePolicy 2025D0090M

Change TypeAdded ICD-10 codes; updated background/evidence; archived prior version

Effective DateSep 1, 2025

Next Review Date

Key ActionDocument migraine diagnosis per ICHD-3 and trials/failures (or contraindications/intolerances) to required prophylactic agents and two CGRP-targeting therapies with required durations.

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.

Archived previous policy version 2024D0090L.

2Phase 3 pivotal trials cited (PROMISE 1 & PROMISE 2)

>=4Required prior prophylactic therapy options listed

12Maximum authorization period (months)

Coverage stance: covered with criteria for Vyepti (eptinezumab-jjmr) as a medically necessary option for the preventive treatment of migraine in adults. FDA indication: Vyepti is a calcitonin gene-related peptide antagonist indicated for the preventive treatment of migraine in adults with a recommended dosage of 100 mg administered by intravenous infusion every 3 months; some patients may benefit from 300 mg IV every 3 months. Policy scope summary: defines medical necessity criteria (diagnosis per ICHD‑3, episodic and chronic migraine thresholds, required prior trials and failures including specific drug classes and CGRP-targeting therapies), continuation/reauthorization requirements, exclusions (e.g., acute migraine treatment, episodic cluster headache), applicable procedure and diagnosis codes, and supporting clinical evidence from pivotal Phase 3 trials. Effective date and last review: Effective: September 1, 2025 (policy number 2025D0090M; version modified) with the Summary of Changes reflecting updated background, clinical evidence, references, and added ICD‑10 codes.

Medically necessary — Initial therapy

Vyepti is medically necessary for the preventive treatment of migraines when ALL of the following criteria are met:

Initial therapy top-level

Diagnosis and migraine frequency
- Option: 4 to 7 migraine days per month with additional requirements
  - AND one of
    Less than 15 headache days per month< 15 headache days per month
    Provider attestation: Provider attests this is the member's predominant headache diagnosis (i.e., primary driver of headaches is not a different, non-migrainous condition)
    Predominant headache diagnosis defined in policy definitions
- Option: >=8 migraine days: Greater than or equal to 8 migraine days per month>= 8 migraine days per month
Required prior prophylactic therapies
- Tricyclic antidepressant option: One of the following tricyclic antidepressants: amitriptyline (Elavil) or nortriptyline (Pamelor)
- Beta-blocker option: One of the following beta-blockers: atenolol, metoprolol, nadolol, propranolol, or timolol
- Candesartan (Atacand)
- Divalproex sodium (Depakote/Depakote ER)
- OnabotulinumtoxinA (Botox) [trial of at least 2 quarterly injections (6 months)]>= 6 months
Required prior CGRP-targeting therapies (non-Medicare)
- Aimovig (erenumab)
- Emgality (galcanezumab) (120 mg strength)
- Nurtec ODT (rimegepant)
- Qulipta (atogepant)
Combination biologic prohibition: 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 is in accordance with the FDA approved labeling (recommended 100 mg IV every 3 months; some patients may benefit from 300 mg IV every 3 months)
Authorization duration: Authorization will be issued for no more than 12 months<= 12 months

Medically necessary — Continuation of therapy

For continuation of therapy, ALL of the following must be met:

Continuation top-level

Positive response: Patient has experienced a positive response to therapy, demonstrated by a reduction in headache frequency and/or intensity
Provider must document response for reauthorization
Combination biologic prohibition: 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 is in accordance with the FDA approved labeling (recommended 100 mg IV every 3 months; some patients may benefit from 300 mg IV every 3 months)
Reauthorization duration:

Not medically necessary / Unproven

Vyepti is unproven and not medically necessary for:

Unproven uses

Acute attack of migraine
Episodic cluster headache

Applicable Codes

Drug HCPCSHCPCSCovered

J3032

Injection, eptinezumab-jjmr, 1 mg

Applicable ICD-10 diagnosis codes (listed for reference)ICD-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

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Provider Actions & Billing Rules

Prior Authorization

Prior authorization required and duration

Authorization will be issued for no more than 12 months for initial therapy; reauthorization for continuation will be issued for no more than 12 months.

J3032

Documentation Required

Document migraine diagnosis and prior therapy failures

Provider must document diagnosis per the International Classification of Headache Disorders, 3rd edition (ICHD-3) and evidence of trials and failures, contraindications, or intolerances to the required prophylactic agents and two CGRP-targeting therapies. Required durations: at least 2 months for non-CGRP prophylactic agents; at least 3 months for prior CGRP-targeting therapies; onabotulinumtoxinA requires a trial of at least 2 quarterly injections (6 months).

Documentation Required

Continuation response documentation

For reauthorization, provider must document a positive response to therapy demonstrated by a reduction in headache frequency and/or intensity.

Denial Risk

Combination biologic CGRP agents prohibited

Claims may be denied if Vyepti is used concomitantly with another biologic CGRP antagonist or inhibitor for preventive treatment of migraines.

J3032
Examples: Aimovig (erenumab), Emgality (galcanezumab), Nurtec ODT (rimegepant), Qulipta (atogepant)

Billing Rule

Dosing must follow FDA labeling

Dosing must follow FDA-approved labeling: recommended 100 mg administered by intravenous infusion every 3 months; some patients may benefit from 300 mg IV every 3 months.

J3032

Clinical Evidence

-8.2 dPROMISE 2: eptinezumab reduced monthly migraine days by 8.2 vs placebo 5.6 (p < 0.0001)

61%PROMISE 2: >=50% response rate 61% vs 39% for placebo (p < 0.0001)

PROMISE 1 (episodic migraine): In a Phase 3 randomized, double‑blind, placebo‑controlled trial (n=888) with IV dosing every 12 weeks, eptinezumab reduced monthly migraine days versus placebo: 300 mg: 4.3 days reduction and 100 mg: 3.9 days reduction compared with 3.2 days for placebo; benefits were statistically significant and onset of clinical benefit was observed by day 1. PROMISE 2 (chronic migraine): In a Phase 3 randomized, double‑blind, placebo‑controlled trial (n=1,072) with IV dosing every 12 weeks, eptinezumab significantly reduced monthly migraine days by 8.2 days versus 5.6 days for placebo (p < 0.0001) and achieved higher responder rates (≥50% reduction: 61% vs 39%). Together these trials support efficacy of eptinezumab for both episodic and chronic migraine. Professional guidance updates (ACP and AHS) are noted in the policy as supporting information for use of CGRP-targeting therapies in migraine prevention.

Background

Background: Vyepti is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that specifically binds the calcitonin gene‑related peptide (CGRP) ligand and blocks its binding to the receptor. The product is FDA‑indicated for the preventive treatment of migraine in adults and is administered by intravenous infusion every 3 months with a recommended dose of 100 mg IV every 3 months and the option that some patients may benefit from 300 mg IV every 3 months. The efficacy of Vyepti as a preventive treatment for both episodic and chronic migraine was demonstrated in the Phase 3 PROMISE 1 and PROMISE 2 trials. Predominant headache diagnosis: provider attestation that the member's primary driver of headaches is migraine rather than another non-migrainous condition.

Revision History

09/01/2025material_changeLatest

Applicable Codes section updated to add ICD-10 diagnosis codes G43.A0, G43.A1, G43.B0, G43.B1, G43.D0, and G43.D1.

09/01/2025non-material_revision

Supporting information updated: Background, Clinical Evidence, and References sections revised to reflect the most current information.

09/01/2025archival

Previous policy version 2024D0090L archived.