Last Review Date: 10/03/2024

Date of Origin: 04/01/2020

Dates Reviewed: 04/2020, 10/2020, 04/2021, 04/2022, 01/2023, 01/2024, 10/2024

1. Length of Authorization

Initial coverage will be provided for 6 months and may be renewed annually thereafter.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• Vyepti 100 mg/mL solution single-dose vial: 3 vials per 84 days

B. Max Units (per dose and over time) [HCPCS Unit]:

• 300 billable units every 84 days

3. Initial Approval Criteria ^1,6,10

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Physician has assessed baseline disease severity utilizing an objective measure/tool (e.g., Headache Impact Test [HIT-6]; monthly headache day [MHD]; Migraine Disability Assessment [MIDAS]; Migraine Physical Function Impact Diary [MPFID]); AND

Universal Criteria ^{1,4,5,7-10,14,15}

• Other causes of headaches have been ruled out; AND
• Not used in combination with prophylactic calcitonin gene-related peptide (CGRP) inhibitors (e.g., erenumab, galcanezumab, fremanezumab, atogepant, rimegepant, etc.) [Note: This does not include CGRP inhibitors if they are being used for acute treatment only (e.g., ubrogepant, rimegepant, zavegepant, etc.)]; AND  
• Patient is not on concurrent treatment with a botulinum toxin (e.g., abobotulinumtoxinA, incobotulinumtoxinA, rimabotulinumtoxinB, etc.) [Note: This does not apply when the botulinum toxin is used for an indication other than prevention of chronic migraines]; AND
• Patient is utilizing prophylactic intervention modalities (e.g., pharmacotherapy, behavioral therapy, physical therapy, etc.); AND

Preventative Treatment of Migraines † ^{1,4,5,7-10,14,15}

• Patient has a diagnosis of chronic migraines defined as 15 or more headache (tension-type-like and/or migraine-like) days per month for > 3 months**; AND
  • • •  
  • Patient has had at least five attacks with features consistent with migraine (with and/or without aura)§; AND
  • On at least 8 days per month for > 3 months:

• Headaches have characteristics and symptoms consistent with migraine§; OR
• Patient suspected migraines are relieved by a triptan or ergot derivative medication; AND

• One of the following apply:
  • Patient has failed at least an 8-week trial of an oral medication for the prevention of migraines (see list of prophylactic medications below for examples ±); OR
  • Patient had an inadequate response (or unable to tolerate) a minimum trial of at least two doses of a botulinum toxin; OR
    • •  
  • Patient has a diagnosis of frequent episodic migraines defined as at least 5 headache attacks lasting 4-72 hours (when untreated or unsuccessfully treated)**; AND
    • Headaches have characteristics and symptoms consistent with migraine without aura§; AND
    • Medication overuse headache has been ruled out by trial and failure of titrating off acute migraine treatments in the past

**NOTE: Patients new to therapy must initiate treatment at the lower dosing regimen of the 100 mg dose before increasing to the 300 mg dose, if required.

† FDA Approved Indication; ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,10

Coverage can be renewed based upon the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe hypersensitivity reactions, etc.; AND
• Disease response as evidenced by the following:

• Reduction in mean monthly headache days (MHD) of at least moderate severity of ≥50% relative to the pretreatment baseline (diary documentation or medical professional attestation); OR
• A clinically meaningful improvement in ANY of the following validated migraine-specific patient-reported outcome measures:
  • • Reduction of ≥5 points when baseline score is 11–20 OR Reduction of ≥30% when baseline score is >20 in the MIDAS scores; OR
    • Reduction of ≥5 points in the MPFID score; OR
    • Reduction of ≥5 points in the HIT-6 score; AND
  • Dose escalation** (up to the maximum dose and frequency specified below) may occur upon clinical review on a case-by-case basis provided that the patient has:
    • Had an initial and then subsequent loss of response to the 100 mg dose; OR
    • Had an inadequate response (e.g., no net decrease in frequency of headaches) to the 100 mg dose

5. Dosage/Administration ^1,11,12

6. Billing Code/Availability Information

HCPCS Code:

• J3032 – Injection, eptinezumab-jjmr, 1 mg: 1 billable unit = 1 mg

NDC:

• Vyepti 100 mg/mL solution for injection; single-dose vial: 67386-0130-xx

7. References

1. Vyepti [package insert].  Bothell, WA; Lundbeck Seattle BioPharm., Inc; August 2024. Accessed September 2024.
2. Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006 Jan 1; 73(1):72-8.
3. Pringheim T, Davenport W, Mackie G, et al. Canadian Headache Society guideline for migraine prophylaxis. Can Jneurol Sci. 2012 Mar; 39(2 Suppl 2):S1-S9.
4. The International Classification of Headache Disorders, 3rd edition. Headache Classification Committee of the International Headache Society (IHS) Cephalalgia. 2018; 38(1):1-211.
5. Garza I, Schwedt TJ. (2024) Chronic Migraine. In Swanson JW (Ed). UpToDate. Last updated: September 12, 2024. Accessed on September 24,2024. Available from https://www.uptodate.com/contents/chronic-migraine
6. American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019 Jan;59(1):1-18. doi: 10.1111/head.13456. Epub 2018 Dec 10.
7. Ashina M, Saper J, Cady R, et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020 Mar;40(3):241-254. doi: 10.1177/0333102420905132. Epub 2020 Feb 19.
8. Cady R, McGill L, Hirman J, et al. Patient Global Impression of Change Related to Improvement in Most Bothersome Symptom Following Treatment With Eptinezumab (S38.009). Neurology Apr 2019, 92 (15 Supplement) S38.009;
9. Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020 Mar 31;94(13):e1365-e1377. doi: 10.1212/WNL.0000000000009169. Epub 2020 Mar 24. Erratum in: Neurology. 2023 Aug 8;101(6):283. PMID: 32209650; PMCID: PMC7274916.
10. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021 Jul;61(7):1021-1039. doi: 10.1111/head.14153. Epub 2021 Jun 23. PMID: 34160823.
11. Apelian R, Boyle L, Hirman J, Asher D. Measuring dose-related efficacy of eptinezumab for migraine prevention: post hoc analysis of PROMISE-1 and PROMISE-2. J Headache Pain. 2022 Apr 18;23(1):48. Doi: 10.1186/s10194-022-01418-8. PMID: 35436857; PMCID: PMC9014586.
12. Chen H, Luo W. Efficacy and safety of eptinezumab 300mg versus 100mg for migraine patients: a meta-analysis of randomized controlled studies. Int J Neurosci. 2022 Sep 29:1-6. doi: 10.1080/00207454.2022.2115906. Epub ahead of print. PMID: 35993143.
13. Toni T, Tamanaha R, Newman B, et al. Effectiveness of dual migraine therapy with CGRP inhibitors and onabotulinumtoxinA injections: case series. Neurol Sci. 2021 Dec;42(12):5373-5376. doi: 10.1007/s10072-021-05547-x. Epub 2021 Aug 18. PMID: 34409517.
14. Charles A, Digre K, Goadsby P, et al. Calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: An American Headache Society position statement update. Headache. 2024; 64: 333-341. doi:10.1111/head.14692
15. Schwedt TJ, Garza I. (2024) Preventive Treatment of Episodic Migraine in Adults. In Swanson JW, Goddeau RP (Ed). UpToDate. Last updated: July 22, 2024. Accessed on September 24,2024. Available from https://www.uptodate.com/contents/preventive-treatment-of-episodic-migraine-in-adults

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/ LCA): N/A