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 Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.
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.
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.
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.
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
Policy: 08.00.15f:Off-label Coverage for Prescription Drugs and/or Biologics
Policy: 08.00.26w:Botulinum Toxin Agents