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DRUG INFORMATION

In accordance with US Food and Drug Administration (FDA) prescribing information, etinezumab-jjmr (VYEPTI™) is administered by intravenous infusion 100 mg every 3 months. Some individuals may benefit from a dosage of 300 mg administered by intravenous infusion every 3 months.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, eptinezumab-jjmr (VYEPTI) is covered under the medical benefits of the Company’s products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Etinezumab-jjmr (VYEPTI™) was approved by the FDA on February 21, 2020, for the preventive treatment of migraine in adult individuals.

PEDIATRIC USE

The safety and effectiveness of etinezumab-jjmr (VYEPTI​) for the preventive treatment of migraine have not been established in the pediatric population.

Description

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Migraine is a complex and incapacitating neurological disease characterized by recurrent episodes of severe headaches typically accompanied by a range of symptoms, including nausea, vomiting, and sensitivity to light or sound. It is estimated to affect approximately 39 million people in the United States and more than 1.3 billion worldwide. Migraine affects women three times more often than men. It is the second leading cause of years lived with disability (YLD) among all diseases, and is the top YLD cause among patients aged 15 to 49 years, according to the Global Burden of Disease study. Migraine affects patients’ lives, their relationships, as well as their activities of daily living. More than 157 million work days are lost each year in the United States because of migraine. Beyond the burden of a migraine attack itself, having migraine increases the risk for other physical and psychiatric conditions.

Eptinezumab-jjmr (VYEPTI) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand. Eptinezumab-jjmr (VYEPTI) binds to CGRP ligand and blocks its binding to the receptor. Eptinezumab-jjmr (VYEPTI) is produced in Pichia pastoris yeast cells by recombinant DNA technology.

PEER-REVIEWED LITERATURE

SUMMARY
The efficacy and safety of etinezumab-jjmr (VYEPTI) was evaluated in two clinical trials: A Multicenter Assessment of ALD403 in Frequent Episodic Migraine (PROMISE-1) and Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine (PROMISE-2). The PROMISE-1 study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study for adult individuals with episodic migraine. Individuals were randomly assigned to eptinezumab-jjmr (VYEPTI) 30 mg, 100 mg, 300 mg, or placebo for up to four intravenous (IV) doses administered every 12 weeks. The primary endpoint was change from baseline in monthly migraine days (MMDs) over weeks 1 to 12. A total of 665 individuals were randomly assigned to either 100 mg (n=221) or 300 mg (n=222) IV eptinezumab (VYEPTI)​ or placebo (n=222) every 3 months for 1 year. Baseline migraine frequency was 8.6 migraine days per month, comparable between groups. Between months 1 and 3, the mean change in migraine days was −3.9 days (P=0.018) and −​4.3 days (P<0.001) for the 100-mg and 300-mg doses, respectively, compared with −3.2 days for the placebo group. During the same period, 49.8% of individuals in the 100-mg group (P=0.009) and 56.3% of individuals in the 300-mg group (P<0.001) experienced 50% or greater reduction in migraine days compared with 37.4% of those in the placebo group. A reduction of 75% or more in migraine days in months 1 through 3 was reported by 22.2% of the 100-mg group, 29.7% of the 300-mg group (P<0.001), and 16.2% of the placebo group.

The PROMISE-2 study was a phase 3, randomized, double-blind, placebo-controlled study evaluating safety and efficacy of two infusions for the preventive treatment of chronic migraine. The primary endpoint was change from baseline in MMDs over weeks 1 through 12. A total of 1072 individuals were randomly assigned and received placebo (N=366), 100 mg eptinezumab-jjmr (VYEPTI) (N=356), or 300 mg eptinezumab-jjmr (VYEPTI) (N=350) every 3 months for 6 months. Individuals were allowed to use and to continue an established stable regimen of acute migraine or headache-preventive medication (except onabotulinumtoxin-A). Individuals with a dual diagnosis of chronic migraine and medication overuse headache attributable to acute medication overuse (triptans, ergotamine, or combination analgesics >10 days per month) were included in the study population. Individuals using opioids or butalbital-containing products greater than 4 days per month were excluded.

In the group of individuals treated with 100 mg eptinezumab-jjmr (VYEPTI)​, changes from baseline in MMDs were −7.7 days (P<0.0001) and −8.1 days (P<0.0001) during the first 3 months (months 1–3) and a second 3 months (months 4–6), respectively. In the more than 75%, migraine response rates (RRs) were 30.9% (month 1; P<0.0001), 26.7% (months 1–3; P=0.0001), and 38.5% (months 4–6). In the 50% or greater, migraine RRs were 57.6% (months 1–3; P<0.0001) and 60.7% (months 4–6).

In the group of individuals treated with 300 mg, changes from baseline in MMDs were −8.2 days (P<0.0001) and −8.8 days (P<0.0001) over the first 3 months and a second 3 months, respectively. In the 75% or greater, migraine RRs were 36.9% (month 1; P<0.0001), 33.1% (months 1–3; P<0.0001), and 42.3% (months 4–6). In the 50% or greater, migraine RRs were 61.4% (months 1–3; P<0.0001) and 63.4% (months 4–6).

In the group of individuals treated with placebo, changes from baseline in MMDs were −5.6 days and −6.1 days over first 3 months and a second 3 months, respectively. In the 75% or greater, migraine RRs were 15.6% (month 1), 15.0% (months 1–3), and 22.7% (months 4–6). In the 50% or greater, migraine RRs were 39.3% (months 1–3) and 44.5% (months 4–6).

The most common adverse reactions (>2% and ≥2% than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity.

Eptinezumab-jjmr (VYEPTI) treatment demonstrated statistically significant improvements compared to placebo for the primary efficacy endpoint in both studies.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

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American Hospital Formulary Service (AHFS). Eptinezumab-jjmr (VYEPTI™)​. AHFS Drug Information 02/25/2026. [LexiComp Web site]. Available at: http://online.lexi.com/lco/action/home# [via subscription only]. Accessed March 2, 2026​.

Ashina M, Saper J, Cady R, et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40(3):241-254.

ClinicalTrials.gov. A Multicenter Assessment of ALD403 in Frequent Episodic Migraine (PROMISE 1). ClinicalTrials.gov Identifier: NCT02559895. First Posted: May 14, 2020; Last Update Posted: May 14, 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT02559895?term=NCT02559895&draw=2&rank=1. Accessed March 2, 2026.

ClinicalTrials.gov. Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine (PROMISE 2). ClinicalTrials.gov Identifier: NCT02974153. First Posted: June 9, 2020; Last Update Posted: June 9, 2020​. Available at: https://clinicaltrials.gov/ct2/show/NCT02974153?term=NCT02974153&draw=2&rank=1. Accessed October 8, 2024.

Elsevier's Clinical Pharmacology Compendium. Eptinezumab-jjmr (VYEPTI™). [MD Consult Web site]. 10/28/2026. Available at: http://www.mdconsult.com [via subscription only]. Accessed March 2, 2026.

Eptinezumab-jjmr (VYEPTI™). [prescribing information]. Bothell, USA: Lundbeck Seattle BioPharmaceuticals, Inc.; 10/2022​​​​. Available at: https://gamifant.com/pdf/Full-Prescribing-Information.pdf. Accessed March 2, 2026.

GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories,1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789-​1858.

Kudrow D, Lipton R, Silberstein S, et al. Eptinezumab for prevention of chronic migraine: results of 2 infusions in the phase 3 PROMISE-2 (Prevention of Migraine via Intravenous Eptinezumab Safety and Efficacy–2) Trial. Neurology. 2019;92(15):2.10-006.

Lexi-Drugs Compendium. Eptinezumab-jjmr. [Lexicomp Online Web site]. 01/02/2026. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 2, 2026.

Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventative therapy. Neurology. 2007;68(5):343-349.

Micromedex® Healthcare Series [Internet database]. Eptinezumab-jjmr. Greenwood Village, CO: Thomson Micromedex. 01/15/2026​​​. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed March 2, 2026.

Migraine Research Foundation. Migraine Facts. Available at https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed March 2, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. (VYEPTI™) eptinezumab-jjmr prescribing information and approval letter [FDA Web site]. Updated 10/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 2, 2026​​.

Steiner TJ, Stovner L J, Vos T, et al. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain. 2018;19(1):17.

Villalón CM, Olesen J. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Ther. 2009;124(3):309-323.​

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