Monoclonal Antibody Therapies for Migraine Prevention

POLICY NUMBER

L.5.01.529

Aimovig (erenumab-aooe)

Ajovy (fremanezumab-vfrm)

Emgality (galcanezumab)

Vyepti (eptinezumab-jjmr)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Migraine is a headache disorder characterized by recurrent moderate to severe headaches with associated symptoms. For patients who experience more than four migraine days per month, preventive treatment may be recommended. Evidence implicates calcitonin gene-related peptide (CGRP) in migraines, and monoclonal antibodies (mAbs) for the CGRP receptor and molecule have been developed for migraine prophylaxis.

Migraine

Approximately 15% of the population have migraines, with a higher prevalence in women than in men. The typical migraine headache is throbbing, unilateral, and aggravated by motion. Migraines are frequently associated with nausea, vomiting, photophobia, and phonophobia, although other neurological symptoms may occur. Migraine attacks can last from several hours to several days and are often preceded by transient neurological symptoms (e.g. visual disturbance) known as migraine aura.Migraines are categorized as episodic or chronic depending on the frequency of attacks. Episodic migraine is defined as migraine or headache for less than 15 days per month and accounts for more than 90% of cases of migraine. Chronic migraine is defined as 15 or more headache days each month, of which at least 8 are migraine days.Migraine was previously thought to be primarily vascular, but recent evidence suggests that sensitization of pain pathways in the central nervous system may be involved. At least three messenger molecules are thought to be involved during migraine attacks: nitric oxide, 5-hydroxytryptamine (5-HT) and CGRP. CGRP is produced in both peripheral and central neurons and is a potent vasodilator. Some preclinical studies suggest that during a migraine, sensory neurons in the trigeminal ganglion release CGRP from their peripherally projecting nerve endings in the meninges.

Treatment

Symptomatic treatment is available for migraine attacks. Other medications such as triptans (5-HT agonists) taken at the onset of a migraine may reduce the severity and duration of the attack. For patients who experience more than 4 migraine days per month, preventive treatment may be recommended. Most of the pharmaceutical agents that reduce migraine attack frequency and severity are antidepressants, anticonvulsants or antihypertensives, and were not developed specifically to prevent migraine. Oral medications approved by the U.S. Food and Drug Administration (FDA) for migraine prophylaxis include topiramate, propranolol, timolol, and valproate. All of these medications have contraindications and side effects that limit their use. Botulinum toxin injections in the head or neck may also be used.

This policy addresses humanized monoclonal antibodies (mAbs) that bind to the CGRP receptor or CGRP molecule and are designed specifically for the prevention of migraine. Unlike oral drug therapy, monoclonal antibodies are not metabolized by the liver can remain in the body for weeks or months. Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Emgality (galcanezumab-gnlm), and Vyepti (eptinezumab-jjmr) are indicated for the preventive treatment of migraine in adults. Emgality (galcanezumab-gnlm) is also indicated for the treatment of episodic cluster headache.

 Related medical policies:

• Botulinum Toxin

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

*Loading dose is 2 autoinjectors or syringes / 30 days 

Initial Criteria

The requested agent will be considered medically necessary when ALL of the following criteria are met:

1. The individual is at least 18 years of age;

2. ONE of the following:

   1. The request is for the preventive treatment of migraines and ALL of the following:

      1. The request is for Aimovig (erenumab-aooe) or Emgality (galcanezumab-gnlm); 

      2. The individual has at least 4 migraine headache days per month; AND

      3. The individual has tried and had an inadequate response to an adequate trial (defined as 60-consecutive days with at least 6 weeks at a generally accepted dose [see Appendix A]) of at least one of the following standard prophylactic pharmacologic therapies in the previous 24 months:

         1. anticonvulsants – divalproex, valproate, topiramate;

         2. beta blockers – atenolol, metoprolol, nadolol, propranolol, timolol;

         3. antidepressants – amitriptyline, duloxetine, nortriptyline, venlafaxine;

         4. antihypertensives – candesartan, lisinopril, verapamil; OR

         5. botulinum toxin; OR

   2. The request is for the treatment of episodic cluster headache and ALL of the following:

      1. The request is for Emgality (galcanezumab-gnlm);

      2. ALL of the following:

         1. The individual has attacks of severe or very severe unilateral orbital, supraorbital, and/or temporal pain [lasting 15 to 180 minutes (when untreated) and occurring at least every other day and up to 8 times per day for the duration of the cluster period] that is associated with ipsilateral conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, forehead and facial sweating, miosis and/or ptosis, eyelid edema, and/or with restlessness/agitation;

         2. The individual has a history of at least two cluster periods lasting 7 days to 1 year (when untreated); AND

         3. The attacks are separated by pain-free remission periods lasting at least 3 months; AND

      3. Individual has tried and had inadequate response to at least one of the following standard prophylactic pharmacologic therapy for cluster headache: lithium, verapamil, melatonin, frovatriptan, prednisone, suboccipital steroid injection, topiramate, and valproate;

3. The individual has not received botulinum toxin injection for migraine prophylaxis in the past 4 months and will not initiate botulinum toxin prophylaxis after starting the requested agent;

4. The individual has been evaluated for and does not have medication overuse headache [see Appendix B];

5. The requested medication will not be used in combination with another CGRP antagonist or inhibitor also being used for the prevention of migraine;

6. The prescriber is or has consulted with a headache specialist (e.g. neurologist; pain management specialist; or specialist with United Council for Neurologic Subspecialties [UCNS] certification);

7. The individual does not have any contraindication(s) to therapy with the requested agent; AND

8. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval:12 months.

Renewal Criteria

The requested agent will be approved for renewal when ALL of the following criteria are met:

1. The individual has been previously approved for the requested agent through the BCBSMS PA process;

2. The prescriber has submitted documentation indicating improvement in migraine prevention (e.g. reduced migraine headache days, reduced migraine frequency, reduction of abortive migraine medication requirement) with the requested agent;

3. The individual has been evaluated for and does not have medication overuse headache;

4. The prescriber is or has consulted with a headache specialist (e.g. neurologist; pain management specialist; or specialist with United Council for Neurologic Subspecialties [UCNS] certification);

5. The requested agent will not be used with concurrent botulinum toxin or with another CGRP antagonist or inhibitor for headache prophylaxis;

6. The individual does not have any FDA labeled contraindication(s) to the requested agent; AND

7. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Length of Approval: 12 months

Ajovy (fremanezumab-vfrm) and Vyepti (eptinezumab-jjmr) are considered not medically necessary as there are other formulary alternatives covered by the Plan for the preventive treatment of migraines.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medication failure is defined as disease progression despite maximally tolerated dose as appropriate for disease state being treated. Adequate trials must be at least 60-consecutive days with at least 6 weeks at a generally accepted dose. Experience of common side effects of medication will not be considered medication failure for the purpose of this review.

Appendix A:  Oral Medications Recommended for Migraine Prevention

  Appendix B: ICHD-3 Criteria for Medication Overuse Headache

1. Headache occurring on >15 days/month in a patient with a preexisting headache disorder;

2. Regular overuse for >3 months of 1 or more drugs that can be taken for acute and/or symptomatic treatment of headache, with medication overuse defined as:

   1. 10 or more days/month with ergot derivatives, triptans, opioids, combination analgesics (e.g., acetaminophen/codeine) or acting as adjuvants (eg, caffeine);

   2. 15 or more days/month for nonopioid analgesics, acetaminophen, and NSAIDs (including aspirin);

3. Not better accounted for by another diagnosis.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

07/24/2019: New policy added.

08/16/2019: Policy statement criteria revised to state that the patient has tried and had an inadequate response to at least an adequate trial of one migraine prophylaxis class (anticonvulsants [divalproex, valproate, topiramate], beta blockers [atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [amitriptyline, venlafaxine]) within previous 24 months as defined by the criteria listed. Added statement that Ajovy (fremanezumab-vfrm) is considered not medically necessary as there are other formulary alternatives covered by the plan for the preventive treatment of migraines. Code Reference section updated to add HCPCS code C9040 as not medically necessary.

09/17/2019: Code Reference section updated to add new HCPCS code J3031, effective 10/01/2019.

10/01/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy section revised regarding medications and quantity limits. Updated initial and renewal evaluation criteria for migraine prevention. Added initial and renewal evaluation criteria for preventative treatment of episodic cluster headache. Sources updated.

08/06/2020: Revised policy statement to include Vyepti (eptinezumab-jjmr) as not medically necessary as there are other formulary alternatives covered by the plan for the preventive treatment of migraines. Policy Guidelines updated to define medication failure. Sources updated. Code Reference section updated to add HCPCS code C9063.

09/23/2020: Code Reference section updated to add new HCPCS code J3032, effective 10/01/2020.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants. Code Reference section updated to remove deleted HCPCS codes C9040 and C9063.

04/01/2024: Policy revised to state that Zavzpret (zavegepant) is considered not medically necessary as there are other formulary alternatives covered by the Plan for the preventive treatment of migraines. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Sources updated.

06/27/2024: Policy updated to extend Length of Approval to 6 months.

07/15/2025: Effective 09/15/2025 - Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy updated to remove Zavzpret (zavegepant). Policy description updated regarding migraines and indications for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Emgality (galcanezumab-gnlm), and Vyepti (eptinezumab-jjmr). Policy section updated to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necesssary criteria revised regarding age requirement, requests for preventive treatment of migraines, treatment of episodic cluster headache, combination therapy, prescriber requirements, contraindications to therapy, and dose requirements. Length of approval updated from 6 months to 12 months. Renewal criteria updated regarding prescriber requirements, combination therapy, and dose requirements. Policy Guidelines updated regarding medication failure, oral medications recommended for migraine prevention, and ICHD-3 criteria for medication overuse headache. Sources updated. Policy update effective 09/15/2025.

SOURCE(S)

1. Blue Cross Blue Shield Association policy # 5.01.29

2. Aimovig prescribing information. Amgen Inc. April 2025. Last accessed April 2025.

3. Ajovy prescribing information. Teva Pharmaceuticals USA, Inc. March 2025. Last accessed April 2025.

4. Charles AC, Digre KB, Goadsby PJ, 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

5. Emgality prescribing information. Eli Lilly and Company. March 2025. Last accessed April 2025.

6. Puledda F, Sacco S, Diener H-C, et al. International Headache Society Global Practice Recommendations for Preventive Pharmacological Treatment of Migraine. Cephalalgia. 2024;44(9). doi:10.1177/03331024241269735

7. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache: The Journal of Head and Face Pain. 2019;59: 1-18. https://doi.org/10.1111/head.13456 .

8. Vyepti prescribing information. Lundbeck Pharmaceuticals LLC. March 2025. Last accessed April 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Not Medically Necessary Codes

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