Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Eptinezumab-jjmr (VYEPTI™)
Policy #:MA08.116a

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Eptinezumab-jjmr (VYEPTI™) is considered medically necessary and, therefore, covered for the preventive treatment of migraine in adult individuals when all of the following criteria are met:

INITIAL CRITERIA
  • A neurologist, headache specialist, or pain specialist has established a diagnosis of episodic (four to 14 headache days per month) or chronic (15 or more headache days per month) migraine
  • Individual is 18 years of age or older
  • Individual had inadequate response or inability to tolerate a four weeks trial of TWO of the following prophylactic medications:
    • Topiramate
    • Divalproex sodium/ valproic acid
    • Beta-blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    • Tricyclic antidepressants: amitriptyline, nortriptyline
    • SNRI antidepressants: venlafaxine, duloxetine
    • Onabotuliniumtoxin A (Botox) for chronic migraines
  • Medication will not be used in combination with another CGRP inhibitor
  • Medication will not be used in combination with onabotuliniumtoxin A (Botox) for chronic migraine

CONTINUATION CRITERIA (AFTER 12 WEEKS OF THERAPY)
Documentation of response to therapy as defined by 50 percent reduction in migraine days per month from baseline (defined as at least four hours duration and moderate intensity)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for etinezumab-jjmr (VYEPTI™) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Policy Guidelines

DRUG INFORMATION

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

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, eptinezumab-jjmr (VYEPTI™) is covered under the medical benefits of the Company’s Medicare Advantage 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

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 impacts 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 impacts patients’ lives, their relationships, as well as their activities of daily living. More than 157 million work days are lost each year in the U.S. due to migraine. Beyond the burden of a migraine attack itself, having migraine increases the risk for other physical and psychiatric conditions.

Eptinezumab-jjmr is a humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand. Eptinezumab-jjmr binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. Eptinezumab-jjmr 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 PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine. 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 randomized to 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 1-12. A total of 665 individuals were randomized to either 100 mg (n = 221) or 300 mg (n = 222) intravenous eptinezumab or placebo (n = 222) every three months for one year. Baseline migraine frequency was 8.6 migraine days per month, comparable between groups. Between months one through three, 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 to -3.2 days for the placebo group. During the same period of time, 49.8 percent of individuals in the 100 mg group (P = 0.009) and 56.3 percent of individuals in the 300 mg group (P <0.001) experienced ≥ 50 percent reduction in migraine days compared to 37.4 percent of those in the placebo group. A reduction of 75 percent or more in migraine days in months one through three was reported by 22.2 percent of the 100 mg group, 29.7 percent of the 300 mg group (P <0.001), and 16.2 percent 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 one through 12. A total of 1072 individuals were randomized and received placebo (N=366), 100 mg VYEPTI (N=356), or 300 mg VYEPTI (N=350) every three months for six months. Individuals were allowed to use and to continue an established stable regimen of acute migraine or headache preventive medication (except onabotulinumtoxinA). Individuals with a dual diagnosis of chronic migraine and medication overuse headache attributable to acute medication overuse (triptans, ergotamine, or combination analgesics greater than 10 days per month) were included in the study population. Individuals using opioids or butalbital-containing products greater than 4 days per month were not allowed.

In the group of individuals treated with 100 mg, changes from baseline in MMDs were −7.7 days (p<0.0001) and −8.1 days (p<0.0001) over first three months (months 1–3) and a second three months (months 4–6), respectively. In the more then 75 percent migraine response rate (RR)s were: 30.9 percent (month one; p<0.0001), 26.7 percent (months 1–3; p=0.0001), and 38.5 percent (months 4–6). In the ≥ 50 percent migraine RRs were: 57.6 percent (months 1–3; p<0.0001) and 60.7 percent (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 first three months and a second three months, respectively. In the ≥75 percent migraine RRs were: 36.9 percent (month one; p<0.0001), 33.1 percent (months 1–3; p<0.0001), and 42.3 percent (months 4–6). In the ≥50 percent migraine RRs were: 61.4 percent (months 1–3; p<0.0001) and 63.4 percent (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 three months and a second three months, respectively. In the ≥75 percent migraine RRs were: 15.6 percent (month 1), 15.0 percent (months 1–3), and 22.7 percent (months 4–6). In the ≥50 percent migraine RRs were: 39.3 percent (months 1–3) and 44.5 percent (months 4–6).

The most common adverse reactions (more then two percent and at least two percent or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity.

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

REFERENCES

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: September 25, 2015; Last Update Posted: September 24, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02559895?term=NCT02559895&draw=2&rank=1. Accessed March 19, 2020.

ClinicalTrials.gov. Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine (PROMISE 2). ClinicalTrials.gov Identifier: NCT02974153. First Posted: November 28, 2016; Last Update Posted: September 19, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT02974153?term=NCT02974153&draw=2&rank=1. Accessed March 19, 2020.

Elsevier's Clinical Pharmacology Compendium.Eptinezumab-jjmr (VYEPTI™). [MD Consult Web site]. 02/27/20. Available at: http://www.mdconsult.com [via subscription only]. Accessed March 19, 2020.

Eptinezumab-jjmr (VYEPTI™). [prescribing information]. Bothell, USA:Lundbeck Seattle BioPharmaceuticals, Inc.; 02/2020. Available at: https://gamifant.com/pdf/Full-Prescribing-Information.pdf. Accessed March 19, 2020.

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. The Lancet. 2018;392(10159):1789–858.

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]. 03/06/2020. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 19, 2020.

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. 02/25/2020. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed March 19, 2020.

Migraine Research Foundation. Migraine Facts. Available at https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed March 23, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. (VYEPTI™) eptinezumab-jjmr prescribing information and approval letter [FDA Web site]. updated 02/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 19, 2020.

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.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)



N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See attachment A




HCPCS Level II Code Number(s)



THE FOLLOWING CODE(S) ARE USED TO REPORT
Eptinezumab-jjmr (VYEPTI™)

C9063 Injection, eptinezumab-jjmr, 1 mg

J3590 Unclassified biologics















Revenue Code Number(s)



N/A


Misc Code

N/A:


N/A


Coding and Billing Requirements


Cross References

Attachment A: Eptinezumab-jjmr (VYEPTI™)
Description: ICD 10 diagnosis list






Policy History

MA08.116a
07/01/2020This policy has been identified for the HCPCS code update, effective 07/01/2020.
The following HCPCS code has been termed from this policy:

C9399 Unclassified drugs or biologics


The following HCPCS code has been added to this policy:

C9063 Injection, eptinezumab-jjmr, 1 mg


MA08.116
05/11/2020This version of the policy will become effective 05/11/2020.

This new policy has been developed to communicate the Company’s coverage criteria for Eptinezumab-jjmr (VYEPTI™).





Version Effective Date: 07/01/2020
Version Issued Date: 07/02/2020
Version Reissued Date: N/A