The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
On February 21, 2020, the U.S Food and Drug Administration (FDA) approved Lundbeck’s Vyepti (eptinezumab-jjmr), a calcitonin gene-related peptide antagonist (CGRP) for the prevention of migraine headaches in adults. Vyepti is the first FDA-approved intravenous (IV) treatment for migraine prevention. Vyepti (eptinezumab-jjmr) is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. Vyepti is the fourth prophylactic anti-CGRP monoclonal antibody (mAb) approved, but it is the first with IV administration, following Amgen’s Aimovig, Teva’s Ajovy, and Eli Lilly’s Emgality.
Vyepti is given every 3 months as a 100 mg intravenous infusion over 30 minutes. The labeling states that some patients may benefit from a dosage of 300 mg. It will be available as a 100 mg/mL solution single-dose vial.
The approval of Vyepti was based upon two randomized, multicenter, placebo-controlled studies, both with 6-month double-blind periods: one study in patients with episodic migraine (Study 1) and one study in patients with chronic migraine (Study 2). The efficacy and safety of Vyepti (eptinezumab-jjmr) was demonstrated in two phase III clinical trials (PROMISE-1 in episodic migraine and PROMISE-2 in chronic migraine).
The clinical trial program demonstrated a treatment benefit over placebo that was observed for both doses of Vyepti (eptinezumab-jjmr) as early as day 1 post-infusion, and the percentage of patients experiencing a migraine was lower for Vyepti (eptinezumab-jjmr) than with placebo for most of the first 7 days. In both studies, patients who received Vyepti experienced fewer migraine days over the first 12 weeks of treatment. In PROMISE-2, data demonstrated that 26.7% (100 mg) to 33.1% (300 mg), compared to 15% of placebo patients, can achieve reduction in migraine days of at least 75% and maintain a sustained migraine improvement through 6 months.
Vyepti was administered by intravenous infusion every 3 months in both studies; however, the primary endpoint was measured at 12 weeks. Study endpoints included a decrease in migraine days.
The safety of Vyepti (eptinezumab-jjmr) was evaluated in 2,076 patients with migraine who received at least one dose of Vyepti (eptinezumab-jjmr). The most common adverse reactions (≥2 percent and at least 2% or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity. In PROMISE-1 and PROMISE-2, 1.9% of patients treated with Vyepti (eptinezumab-jjmr) discontinued treatment due to adverse reactions. Adverse reactions have included angioedema, urticaria, facial flushing, and rash. Vyepti (eptinezumab-jjmr) is contraindicated in anyone with serious hypersensitivity to eptinezumab-jjmr or any of the excipients.
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
2. When considered medically necessary, Vyepti (eptinezumab-jjmr) will be approved initially for 6 months based on FDA-approved labeling:
1. Vyepti (eptinezumab-jjmr) will be considered medically necessary when ALL of the following are met:
· The requested agent is being used for ONE of the following diagnoses as preventative treatment of migraines:
· The prescriber is a specialist in the area of the patient’s diagnosis (e.g. neurologist) or has consulted with a specialist in the area of the patient’s diagnosis
o Chronic migraines (documentation required) and the member meets ALL of the following:
o Episodic migraines (documentation required) and the member meets ALL of the following:
§ ≥15 headache days per month of migraine-like or tension-like headache for a minimum of 3 months AND
§ ≥8 migraine headache days per month for a minimum of 3 months
§ Member meets ONE of the following:
· Member's migraine headaches last >12 hours OR
· Member has > 4 migraine days per month OR
· Member’s migraine attacks cause significant disability or diminished quality of life despite appropriate therapy with acute agents only OR
· Member has tried and failed, or has contraindications to acute therapies OR
· Member is at risk of medication overuse headache without preventative therapy; AND
· Member is 18 years of age or older
· Medication overuse headache has been ruled out
· Member has tried and had an inadequate response to at least two migraine prophylaxis class (i.e. anticonvulsants [divalproex, valproate, topiramate], beta blockers [atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [amitriptyline, venlafaxine], candesartan) after an adequate trial as defined by BOTH of the following:
· Member will not be using botulinum toxin for headache prophylaxis after starting the requested agent
o The trial length was at least 6 weeks at generally accepted doses AND
o The patient was ≥80% adherent to the prophylaxis agent during the trial OR
o The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL of the above agents
· Member will not be using another CGRP (calcitonin gene-related peptide antagonist) in combination with the requested agent
· Member does not have any FDA labeled contraindications to the requested agent
- 100 mg or 300mg administered by intravenous infusion every 3 months
- When up-dosing to 300mg is deemed medically necessary, member must have trial and inadequate response of 100mg dosing
[INFORMATIONAL NOTE: as per the FDA labeled package insert, dosing section: some patients may benefit from a dosage of 300 mg administered by intravenous infusion every 3 months.]
3. Continued use will be approved for 12 months (at every 3 month dosing) when the following criteria are met:
4. The use of Vyepti (eptinezumab-jjmr) is considered investigational for all other indications.
- Member has been approved for the requested agent previously through the plan
- The requested agent is being used for migraine prophylaxis
- The prescriber has provided information indicating improvement in migraine prevention (e.g. reduced migraine headache days, reduced migraine frequency, reduced use of acute abortive migraine medication) with the requested agent
- Member will not be using botulinum toxin for headache prophylaxis while using the requested agent
- Member will not be using the requested agent in combination with another CGRP agent
- Member does not have any FDA labeled contraindications to the requested agent and there are no unacceptable toxicities after using the requested drug
- If the requested dose has been up-dosed to 300mg, member must have trial and inadequate response of 100mg dosing
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
1. Vyepti (eptinezumab-jjmr) [prescribing information]. Bothell, WA: Lundbeck Seattle BioPharmaceuticals, Inc. February 2020.
2. Clinicaltrials.gov. Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine (PROMISE 2). NCT02974153. Available at https://clinicaltrials.gov/ct2/show/NCT02974153.
3. Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020 Mar 24.
4. Clinicaltrials.gov. A Multicenter Assessment of ALD403 in Frequent Episodic Migraine (PROMISE 1). NCT02559895. Available at: https://clinicaltrials.gov/ct2/show/NCT02559895
5. AMCP Dossier. Vyepti (eptinezumab-jjmr). Lundbeck. March 13, 2020.
6. Vyepti (eptinezumab-jjmr). IPD Analytics. New Drug Review. March 2020.
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy