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ph-1033

Calcitonin Gene-Related Peptide (CGRP) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1033

This program applies to Blue Partner, Commercial, GenPlus, NetResults A, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
07-01-2024

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Aimovig® (erenumab-aooe) Subcutaneous autoinjector Subcutaneous prefilled syringe	Preventive treatment of migraine in adults		1
AJOVY® (fremanezumab) Subcutaneous autoinjector Subcutaneous prefilled syringe	Preventive treatment of migraine in adults		2
Emgality® (galcanezumab-gnlm) Subcutaneous prefilled pen Subcutaneous prefilled syringe	Preventive treatment of migraine in adults Treatment of episodic cluster headache in adults		3
Nurtec ODT® (rimegepant sulfate) Orally disintegrating tablet	Acute treatment of migraine with or without aura in adults Preventive treatment of episodic migraine in adults		19
QULIPTA® (atogepant) Tablet	Preventive treatment of migraine in adults		21
UBRELVY® (ubrogepant) Tablet	Acute treatment of migraine with or without aura in adults Limitations of Use: UBRELVY is not indicated for the preventive treatment of migraine.		20
Zavzpret™ (zavegepant) Nasal spray	Acute treatment of migraine with or without aura in adults Limitations of Use: Zavpret is not indicated for the preventive treatment of migraine.		23

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Migraine and Cluster Headache Management

Migraine is a common disabling primary headache disorder with high prevalence, ranking second globally in terms of years lost to disability.(7) Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia. Migraines can present with or without aura, unilateral fully reversible visual, sensory, or other central nervous system symptoms that usually develop gradually and are most-often followed by headache and associated migraine symptoms.(5)

The International Classification of Headache Disorders 3rd Edition (ICHD-3) Diagnostic Criteria:(5)

Indication	Diagnostic Criteria
Migraine without aura	At least five attacks fulfilling criteria B-D Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated) Headache has at least TWO of the following: unilateral location pulsating quality moderate to severe pain intensity aggravation by causing avoidance of routine physical activity During headache at least ONE of the following: nausea and/or vomiting photophobia and phonophobia Not better accounted for by another ICHD-3 diagnosis
Migraine with aura	At least two attacks fulfilling criteria B and C One or more of the following fully reversible aura symptoms: visual sensory speech and/or language motor brainstem retinal At least THREE of the following: at least one aura symptom spreads gradually over 5 minutes or more two or more aura symptoms occur in succession each individual aura symptom lasts 5-60 minutes at least one aura symptom is unilateral at least one aura symptom is positive the aura is accompanied, or followed within 60 minutes, by headache Not better accounted for by another ICHD-3 diagnosis
Chronic Migraine	Headache (migraine-like or tension-type-like) on greater than or equal to 15 days/month for greater than 3 months AND fulfilling B and C Occurring in patient who has had at least 5 attacks fulfilling criteria B-D for migraine without aura (noted above) and/or criteria B and C for migraine with aura (noted above) On greater than or equal to 8 days/month for greater than 3 months, fulfilling any of the following: criteria C and D for migraine without aura (noted above) criteria B and C for migraine with aura (noted above) believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative Not better accounted for by another ICHD-3 diagnosis
Cluster Headache	At least 5 attacks fulfilling criteria B-D Severe to very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes (untreated) At least one of the following: At least one of the following signs or symptoms, ipsilateral to the headache conjunctival injection and/or lacrimation nasal congestion and/or rhinorrhea eyelid edema forehead and facial sweating miosis and/or ptosis Sense of restlessness or agitation Occurring with frequency between one every other day and 8 per day Not better accounted for by another ICHD-3 diagnosis
Episodic Cluster Headache	Attacks fulfilling criteria for Cluster Headache (noted above) occurring in bouts (cluster periods) At least two cluster periods lasting 7 days to 1 years (untreated) and separated by pain-free remission periods of at least 3 months

The IHS notes that cluster periods usually last between 2 weeks and 3 months.(5)

Migraine prevention may be of benefit in those with the following:(7,8,22)

Frequent or long-lasting migraine headaches (greater than 4 headaches/month or headaches lasting greater than 12 hours)
Attacks interfere significantly with patients' daily routines despite acute treatment
Contraindication to acute therapies
Failure of acute therapies
Adverse effects with acute therapies
Risk of medication overuse headache (MOH)
Patient preference

The American Headache Society (AHS) and the American Academy of Neurology (AAN) suggest the following agents for the prevention of migraine:(4)

Established as effective (Level A)
- Antiepileptic drugs (AEDs)
  - Divalproex
  - Valproate
  - Topiramate
- Beta blockers
  - Metoprolol
  - Propranolol
  - Timolol
- Triptans
  - Frovatriptan for short term menstrually associated migraines (MAMs) prevention
Probably effective (Level B)
- Antidepressants
  - Amitriptyline
  - Venlafaxine
- Beta blockers
  - Atenolol
  - Nadolol
- Triptans
  - Naratriptan, zolmitriptan for short term MAMs prevention

The 2021 American Headache Society Consensus Statement recommends the following indications for initiating treatment acute treatment with gepants and ditans agents:(22)

Prescribed by a licensed clinician
Patient is at least 18 years of age
Diagnosis of ICHD-3 migraine with aura, migraine without aura, or chronic migraine
Either of the following:
- Contraindication to or inability to tolerate triptans
- Inadequate response to two or more oral triptans, as determined by either of the following:
  - Validated acute treatment patient-reported outcoming questionnaire (mTOQ, Migraine-ACT, PPMQ-R, FIS, PGIC)
  - Clinician attestation

Lasmiditan is a selective serotonin 5HT-1F receptor agonist that lacks vasoconstrictor activity. Lasmiditan is structurally different than triptans and therefore constitutes a new class of drugs called “ditans”.(22) Ditans are selective for the 5HT-1F receptor and its mechanism of action is neuronal without evidence of vasoactive effects.(27) Triptans non-specifically bind to the 5HT-1B and 5HT-1D receptors and with varying affinity bind the 5HT-1F receptors, causing direct vascular vasoconstriction. The safety, tolerability, and efficacy of co-administering lasmiditan with a triptan or a gepant has not been assessed.(22) Patients who do not respond to initial therapy with a triptan, may benefit from a second triptan or different therapy such as use of a gepant (ubrogepant or rimegepant) or a ditan (lasmiditan).(7)

The 2021 American Headache Society Consensus Statement recommends the following indications for initiating treatment with a Calcitonin Gene-Related Peptide (CGRP) agent:(22)

Prescribed by a licensed clinician
Patient is at least 18 years of age
ONE of the following:
- Diagnosis of migraine with or without aura (4-7 monthly headache days) and both of the following:
  - Inability to tolerate (due to side effects) or inadequate response to an 8-week trial of at least two of the following:
    - Topiramate
    - Divalproex sodium/valproate sodium
    - Beta blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    - Tricyclic antidepressant: amitriptyline, nortriptyline
    - Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    - Other Level A or B treatment according to AAN-AHS guideline
  - At least moderate disability (Migraine Disability Assessment Questionnaire [MIDAS] greater than or equal to 11, Headache Impact Test-6 [HIT]-6 greater than 50)
- Diagnosis of migraine with or without aura (8-14 monthly headache days[MHDs]) and inability to tolerate (due to side effects) or inadequate response to an 8-week trial of at least two of the following:
  - - Topiramate
    - Divalproex sodium/valproate sodium
    - Beta blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    - Tricyclic antidepressant: amitriptyline, nortriptyline
    - Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    - Other Level A or B treatment according to AAN-AHS guideline
- Diagnosis of chronic migraine and one of the following:
  - Inability to tolerate (due to side effects) or inadequate response to an 8-week trial of at least two of the following:
    - Topiramate
    - Divalproex sodium/valproate sodium
    - Beta blocker: metoprolol, propranolol, timolol, atenolol, nadolol
    - Tricyclic antidepressant: amitriptyline, nortriptyline
    - Serotonin-norepinephrine reuptake inhibitor: venlafaxine, duloxetine
    - Other Level A or B treatment according to AAN-AHS guideline
  - Inability to tolerate or inadequate response to a minimum of two quarterly injection (6 months) of onabotulinum toxin A

The Medical Letter Treatment Guidelines (2023) and Institute for Clinical Systems Improvement Guideline Diagnosis and Treatment of Migraine Headache - Drugs for Migraine states that a triptan is the drug of choice for moderate to severe migraine. The short-acting oral serotonin (5-HT1B/1D) receptor agonists (triptans) sumatriptan (IMITREX, and others), almotriptan (Axert, and generics), eletriptan (RELPAX), rizatriptan (Maxalt, and generics), and zolmitriptan (Zomig, and generics) are similar in efficacy.(24,25) Onset of pain relief generally occurs 30-60 minutes after administration. The longer-acting oral triptans naratriptan (Amerge, and generics) and frovatriptan (Frova, and generics) have a slower onset of action and lower initial response rate than other triptans, but they are better tolerated. Patients with migraine who have nausea or vomiting may not be able to take an oral triptan. Intranasal triptan formulations have a more rapid onset of action than oral tablets, but their efficacy is partially dependent on GI absorption of the portion of the dose that is swallowed. Use of sumatriptan nasal powder (ONZETRA Xsail) results in a faster rise in sumatriptan plasma concentrations and higher peak concentrations than use of a similar dose of sumatriptan nasal spray, suggesting that a larger portion of the dose is absorbed intranasally with the powder. Subcutaneously administered sumatriptan relieves pain faster (in about 10 minutes) and more effectively than other triptan formulations, but it causes more adverse effects.(25)

American Headache Society (AHS) (2015): Triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan [oral, nasal spray, injectable, transcutaneous patch], zolmitriptan [oral and nasal spray]) are effective (Level A) and considered by AHS guidelines (2015) to be the gold standard for acute treatment of moderate to severe migraine headaches.(8) Dihydroergotamine is recommended for use as a second- or third-line therapy for select patients or for those with refractory migraine. Intranasal dihydroergotamine has strong evidence of effectiveness but more adverse effects than triptans because of its decreased receptor specificity.(18) An assessment of new migraine treatments by the AHS (2018; updated 2021) reaffirms previous migraine guidelines. The update lists triptans, dihydroergotamine, the oral gepants (Nurtec ODT [rimegepant] and UBRELVY [ubrogepant]), and REYVOW (lasmiditan) as effective treatment of moderate or severe acute attacks and mild to moderate attacks that respond poorly to non-specific nonsteroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics, acetaminophen, or caffeinated combinations (e.g., aspirin/acetaminophen/caffeine). The recommendation remains that prescribers must consider medication efficacy and potential medication-related adverse effects, potential adverse events, patient-specific contraindications to use with a particular medication, and drug-drug interactions when prescribing acute medications for migraine.(7,8,22)

The American Academy of Neurology (AAN) 2010 Guideline: Acute and preventive pharmacologic treatment of Cluster Headache (CH) state that sumatriptan subcutaneous injection and zolmitriptan nasal spray are first line-options for acute treatment of CH.(12,24) Since the publication of the 2010 AAN review, and re-reviewed in 2016, there is no new data from randomized, double-blind, controlled trials that contribute to determining the efficacy or safety for a number of acute treatments, including specifically sumatriptan and zolmitriptan. For acute treatment, sumatriptan subcutaneous, zolmitriptan nasal spray, and high flow oxygen remain the treatments with a Level A recommendation.(26) Guidelines suggest that prophylactic therapy should be started and continued for the duration of the CH period. Prophylactic pharmacological therapy includes verapamil, corticosteroids, lithium, topiramate, melatonin, gabapentin, valproic acid, ergotamine, and capsaicin. Verapamil is commonly considered the first option for prophylactic therapy in practice.(10,11,12) Corticosteroids can be used as transitional or bridging therapy until another prophylaxis agent is established.(10) Corticosteroids may be used by some practitioners for short periods of CH.(11,12) The American Academy Neurology lists the following agents as option that maybe considered or should be advised as preventative treatments:

Civamide
Suboccipital steroid injection
Melatonin
Verapamil
Lithium

The European Headache Federation and WHO consensus article (2019) states the following:(13)

Individuals with migraine headaches should always be managed in primary care with the exception being chronic migraine, which likely requires specialist management
Any headache not responding satisfactorily in primary care or chronic migraine, should be referred to a specialist
In adults and children, regular high frequency use (greater than 2 day/week) of acute medication risks the development of MOH
Treatment of episodic acute migraine headaches should be approached in a step wise manner and should treat three attacks at each step before moving to the next step if needed:
- Step 1:
  - Use non-opioid analgesics, plus an antiemetic when needed
- Step 2 for adults:
  - Use triptan products
  - Triptans should not be used regularly for 10 or more days per month to avoid the risk of MOH
  - Triptan efficacy is highly variable between individuals, so patients should try different triptans and formulations. Sumatriptan subcutaneous injection should be considered when all other triptans are ineffective.
  - When vomiting is present, zolmitriptan nasal spray or sumatriptan subcutaneous injection may be preferred
- Step 2 for children and adolescents:
  - Failure of Step 1 in children should lead to specialist referral. No specific anti-migraine drugs have shown efficacy in children under 12 years of age.
  - Failure of Step 2 in adolescents (12-17 years of age), the following have shown efficacy and are approved:
    - Sumatriptan nasal spray
    - Zolmitriptan nasal spray
Episodic migraine prophylaxis:
- Indication for migraine prophylaxis include:
  - Attacks cause disability on two or more days per month, and
  - Acute therapy has been optimized but does not prevent this, or is poorly tolerated, or there is a risk of over-frequent use of acute therapy, even when it is effective, and
  - Patient is willing to take daily medication
  - Failure of acute therapy is an indication for migraine prophylaxis
  - For children, frequent absence from school is an additional indication for prophylaxis
- Migraine prophylaxis agents may take 2-3 months to show efficacy
- Children requiring prophylactic medication should be referred to a specialist
- Medications which are effective in adult prophylaxis of episodic migraine include:
  - Beta blockers:
    - Atenolol, bisoprolol, metoprolol, propranolol
  - Amitriptyline
  - Topiramate
  - Candesartan
  - Sodium valproate
  - Flunarizine
  - CGRP
- Onabotulinum toxin A is not effective in episodic migraine and not recommended
- When prophylaxis therapy fails:
  - May be due to subtherapeutic dosage or duration of therapy
  - Failure of one therapy does not predict the failure of another therapy in a different class
  - Review of the following are recommended:
    - Diagnosis
    - Adherence
    - Other medications, especially for MOH causes
  - The prophylaxis therapy should be discontinued if it fails to show clear benefit
  - If all prophylaxis therapies fail, a specialist should be referred
Chronic migraine management:
- Chronic migraine patients should be referred to a specialist
- Medications with efficacy in chronic migraine include:
  - Topiramate
  - Onabotulinum A
  - CGRP
Cluster Headache management:
- Patients should be referred to a specialist
- Acute therapies include:
  - Triptans:
    - Sumatriptan subcutaneous injection
    - Sumatriptan nasal spray
    - Zolmitriptan nasal spray
  - Oxygen
- Transition and maintenance therapies include:
  - Prednisone
  - Greater occipital nerve blockade
  - Verapamil
  - Lithium carbonate
  - Topiramate
- Neuromodulation is another treatment option
- Failure of one prophylactic therapy does not predict the failure of other therapies
- Combination prophylaxis therapy can be considered though the potential for toxicity is high
- Long-term prophylaxis therapy may need to be continued

The European Headache Federation guideline states the following on combining migraine prophylaxis therapy:(14)

In episodic migraine, guidelines suggest to stop oral prophylaxis migraine agents before starting CGRPs, unless the patient previously had chronic migraine prior to prophylaxis. In such patients, the suggestion is to add CGRP to the ongoing oral prophylaxis therapy
In chronic migraine, guidelines suggestto add CGRP to ongoing oral prophylaxis therapy
In chronic migraine patients on onabotulinum A therapy and are receiving inadequate treatment response, guidelines suggestto stop onabotulinum A therapy before starting CGRPs
In patients with chronic migraine who are on treatment with CGRP and may benefit from additional prevention, guidelines suggest to add on oral preventative agents
In patients with medication overuse, guidelines suggestto use CGRPs before or after withdrawal of acute medications

The clinical trials referenced in FDA labeled package inserts for the preventative CGRP agents excluded patients that had received botulinum toxin within 4 months prior to receiving the CGRP agent.(15,16,17) However the 2021 American Headache Society consensus statement states that CGRP monoclonal antibody treatment (e.g., eptinezumab-jjmr, erenumab, fremanezumab, galcanezumab) may be added to greater than or equal to one established preventative treatment, based on clinical judgement, in adults who meet the ICHD-3 criteria for the following conditions:(5,22)

Migraine with/without aura (4‒7 monthly migraine days [MMDs]) with at least moderate disability (Migraine Disability Assessment greater than or equal to 11 or 6-item Headache Impact Test greater than 50) and failure of an 8-week trial of greater than or equal to 2 preventive treatments with established efficacy (e.g., topiramate, divalproex sodium, beta-blocker, tricyclic antidepressant, and others)
Migraine with/without aura (8–14 MMDs) and failure of an 8-week trial of greater than or equal to 2 established preventive treatments
Chronic migraine (greater than or equal to 15 MMDs) with any level of disability and either failure of an 8-week trial of greater than or equal to two established preventive treatments or inadequate tolerability or response to onabotulinum toxin A for two quarterly injections

Medication overuse headache (MOH)

The European Headache Federation and WHO consensus article (2019) states the following:(13)

- Prevention is preferred
- The four objectives of management are:
  - Stop the overused medication
  - Recovery from MOH
  - Review and reassess the underlying headache disorder
  - Prevent relapse while allowing acceptable use of medications
- Comorbidities may require management

Safety

Atogepant is contraindicated in patients with a history of hypersensitivity to atogepant or to any of the components of QULIPTA.(21)

Erenumab-aooe is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients.(1)

Fremanezumab-vfrm is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm to any of the excipients.(2)

Galcanezumab-gnlm is contraindicated in patients with serious hypersensitivity to galcanezumab-gnlm to any of the excipients.(3)

Rimegepant is contraindicated in patients with a history of hypersensitivity reaction to rimegepant, Nurtec ODT, or to any of its components.(19)

Ubrogepant is contraindicated in the following:(20)

Concomitant use with strong CYP3A4 inhibitors
History of serious hypersensitivity to ubrogepant or any components of UBRELVY

Zavegepant is contraindicated in patients with a history of hypersensitivity reaction to zavegepant or to any of the components of Zavzpret.(23)

REFERENCES

Number	Reference
1	Aimovig prescribing information. Amgen Inc. May 2023.
2	AJOVY prescribing information. Teva Pharmaceuticals USA, Inc. October 2022.
3	Emgality prescribing information. Eli Lilly. March 2021.
4	Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-1345
5	ICHD-3 Classification. International Headache Society. 2018.
6	Reference no longer used.
7	The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. American Headache Society. 12/10/2018. Available at https://onlinelibrary.wiley.com/doi/10.1111/head.13456.
8	Marmura M, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache. 2015;55:3–20.
9	Reference no longer used.
10	Weaver-Agostoni, J. Cluster headache. American Family Physician. 2013 Jul 15; 88(2): 122-128.
11	Goadsby PJ. Information for Health Care Professionals: Treatments for Cluster Headache. American Headache Society. 2018 June. https://americanheadachesociety.org/wp-content/uploads/2018/06/Goadsby-Cluster-Headache.docx.
12	Francis GJ, Becker WJ, Pringsheim TM. Acute and preventative pharmacologic treatment of cluster headache. August 03, 2010; 75 (5).
13	Steiner TJ, Jensen R, Katsarava Z, et al. Aids to management of headache disorders in primary care (2nd edition). Journal of Headache and Pain. 2019; 20:57. https://doi.org/10.1186/s10194-018-0899-2.
14	Sacco S, Bendtsen L, Ashina M, et al. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. The Journal of Headache and Pain. (2019) 20:6.
15	Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun;16(6):425-434. doi: 10.1016/S1474-4422(17)30083-2.
16	Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018 Dec 11;91(24):e2211-e2221. doi: 10.1212/WNL.0000000000006640.
17	Lipton RB, Cohen JM, Gandhi SK, Yang R, Yeung PP, Buse DC. Effect of fremanezumab on quality of life and productivity in patients with chronic migraine. Neurology. 2020 Aug 18;95(7):e878-e888. doi: 10.1212/WNL.0000000000010000.
18	Mayans L, Walling A. Acute Migraine Headache: Treatment Strategies. Am Fam Physician. 2018; 97(4): 243-251.
19	Nurtec ODT prescribing information. Pfizer Laboratories Div Pfizer Inc. April 2023.
20	UBRELVY prescribing information. Allergan, Inc. June 2023.
21	QUILIPTA prescribing information. AbbVie Inc. June 2023.
22	Ailani J, Burch RC, Robbins MS, on behalf of the 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;61(7):1021-1039.
23	Zavzpret prescribing information. Pfizer Laboratories Div Pfizer Inc. March 2023.
24	Beithon J, Gallenberg M, Johnson K, Kildahl P, Krenik J, Liebow M, Linbo L, Myers C, Peterson S, Schmidt J, Swanson J. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Headache. ICSI. Updated January 2013. https://www.icsi.org/wp-content/uploads/2019/01/Headache.pdf.
25	Drugs for Migraine. Med Lett Drugs Ther. 2023 Jun 12; 65(1678):89-96. doi:10.58347/tml.2023.1678a.
26	Robbins MS, Starling AJ, Pringsheim TM, Becker WJ, Schwedt TJ. Treatment of Cluster Headache: The American Headache Society Evidence-Based Guidelines. Headache. 2016; 56: 1093-106. doi:10.1111/head.12866.
27	Oswald JC, Schuster NM. Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. J Pain Res. 2018; 11: 2221-2227.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Zavzpret	zavegepant hcl nasal spray	10 MG/ACT	M ; N ; O ; Y	N
Qulipta	atogepant tab	10 MG ; 30 MG ; 60 MG	M ; N ; O ; Y	N		1. Preferred
Aimovig	erenumab-aooe subcutaneous soln auto-injector	140 MG/ML ; 70 MG/ML	M ; N ; O ; Y	N		1. Preferred
Ajovy	fremanezumab-vfrm subcutaneous soln auto-inj	225 MG/1.5ML	M ; N ; O ; Y	N		1. Preferred
Ajovy	fremanezumab-vfrm subcutaneous soln pref syr	225 MG/1.5ML	M ; N ; O ; Y	N		1. Preferred
Emgality	galcanezumab-gnlm subcutaneous soln auto-injector	120 MG/ML	M ; N ; O ; Y	N		1. Preferred
Emgality	galcanezumab-gnlm subcutaneous soln prefilled syr	100 MG/ML ; 120 MG/ML	M ; N ; O ; Y	N		1. Preferred
Nurtec	rimegepant sulfate tab disint	75 MG	M ; N ; O ; Y	N		1. Preferred
Ubrelvy	ubrogepant tab	100 MG ; 50 MG	M ; N ; O ; Y	N		1. Preferred

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Nurtec	Rimegepant Sulfate Tab Disint 75 MG	75 MG	16	Tablets	30	DAYS
Qulipta	Atogepant Tab	10 MG	30	Tablets	30	DAYS
Qulipta	Atogepant Tab	30 MG	30	Tablets	30	DAYS
Qulipta	Atogepant Tab	60 MG	30	Tablets	30	DAYS
Ubrelvy	Ubrogepant Tab 100 MG	100 MG	16	Tablets	30	DAYS
Ubrelvy	Ubrogepant Tab 50 MG	50 MG	16	Tablets	30	DAYS
Zavzpret	zavegepant hcl nasal spray	10 MG/ACT	8	Devices	30	DAYS
Aimovig	Erenumab-aooe Subcutaneous Soln Auto-Injector 140 MG/ML	140 MG/ML	1	Injection Device	28	DAYS
Aimovig	Erenumab-aooe Subcutaneous Soln Auto-Injector 70 MG/ML	70 MG/ML	1	Injection Device	28	DAYS
Emgality	Galcanezumab-gnlm Subcutaneous Soln Auto-Injector 120 MG/ML	120 MG/ML	1	Injection Device	28	DAYS
Emgality	Galcanezumab-gnlm Subcutaneous Soln Prefilled Syr 100 MG/ML	100 MG/ML	9	Syringes	180	DAYS
Emgality	Galcanezumab-gnlm Subcutaneous Soln Prefilled Syr 120 MG/ML	120 MG/ML	1	Syringe	28	DAYS
Ajovy	Fremanezumab-vfrm Subcutaneous Soln Auto-inj 225 MG/1.5ML	225 MG/1.5ML	3	Injection Devices	84	DAYS
Ajovy	Fremanezumab-vfrm Subcutaneous Soln Pref Syr 225 MG/1.5ML	225 MG/1.5ML	3	Syringes	84	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Zavzpret	zavegepant hcl nasal spray	10 MG/ACT	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Aimovig	erenumab-aooe subcutaneous soln auto-injector	140 MG/ML ; 70 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ajovy	fremanezumab-vfrm subcutaneous soln auto-inj	225 MG/1.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ajovy	fremanezumab-vfrm subcutaneous soln pref syr	225 MG/1.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Emgality	galcanezumab-gnlm subcutaneous soln auto-injector	120 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Emgality	galcanezumab-gnlm subcutaneous soln prefilled syr	100 MG/ML ; 120 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Nurtec	rimegepant sulfate tab disint	75 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Qulipta	atogepant tab	10 MG ; 30 MG ; 60 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ubrelvy	ubrogepant tab	100 MG ; 50 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Nurtec	Rimegepant Sulfate Tab Disint 75 MG	75 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Qulipta	Atogepant Tab	60 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Qulipta	Atogepant Tab	10 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Qulipta	Atogepant Tab	30 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ubrelvy	Ubrogepant Tab 100 MG	100 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ubrelvy	Ubrogepant Tab 50 MG	50 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Zavzpret	zavegepant hcl nasal spray	10 MG/ACT	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Aimovig	Erenumab-aooe Subcutaneous Soln Auto-Injector 140 MG/ML	140 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Aimovig	Erenumab-aooe Subcutaneous Soln Auto-Injector 70 MG/ML	70 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Emgality	Galcanezumab-gnlm Subcutaneous Soln Auto-Injector 120 MG/ML	120 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Emgality	Galcanezumab-gnlm Subcutaneous Soln Prefilled Syr 100 MG/ML	100 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Emgality	Galcanezumab-gnlm Subcutaneous Soln Prefilled Syr 120 MG/ML	120 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ajovy	Fremanezumab-vfrm Subcutaneous Soln Auto-inj 225 MG/1.5ML	225 MG/1.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ajovy	Fremanezumab-vfrm Subcutaneous Soln Pref Syr 225 MG/1.5ML	225 MG/1.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Indication	Preferred Agent(s)	Non-Preferred Agent(s)	Stand Alone Target Agent(s)
Chronic Migraine Prophylaxis	Aimovig, Ajovy, Emgality
Episodic Migraine Prophylaxis	Aimovig, Ajovy, Emgality, Nurtec, Qulipta
Episodic Cluster Headaches	Emgality
Acute Migraine Treatment	Nurtec, Ubrelvy		Zavzpret

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

ONE of the following:
1. The requested agent is being used for migraine prophylaxis AND ALL of the following:
  1. ONE of the following:
    1. The patient has at least 15 headache days per month of migraine-like or tension-like headache for a minimum of 3 months (chronic migraine) AND ALL of the following:
      1. The patient has at least 8 migraine headache days per month for a minimum of 3 months AND
      2. The patient will NOT be using the requested agent in combination with another prophylactic use CGRP AND
      3. The requested agent and strength are FDA labeled for chronic migraine prophylaxis OR
    2. The patient has less than 15 headache days per month (episodic migraine) AND ALL of the following:
      1. ONE of the following:
        
        The patient has greater than 4 migraine headache days per month OR
        
        The patient’s migraine headaches last greater than 12 hours OR
        
        The patient’s migraine attacks cause significant disability or diminished quality of life despite appropriate therapy with acute agents only OR
        
        The patient has contraindications to acute therapies OR
        
        The patient has tried and received inadequate response to acute therapies OR
        
        The patient has serious side effects to acute therapies OR
        
        The patient is at risk of medication overuse headache without preventative therapy AND
      2. The patient will NOT be using the requested agent in combination with another prophylactic use CGRP agent AND
      3. The requested agent and strength are FDA labeled for episodic migraine prophylaxis AND
  2. ONE of the following:
    1. The patient has ONE of the following to at least one migraine prophylaxis class (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan):
      1. A trial and inadequate response after an adequate trial as defined by BOTH of the following:
        
        The trial length was at least 8 weeks at generally accepted doses AND
        
        The patient was greater than or equal to 80% adherent to the prophylaxis agent during the trial OR
      2. The patient has an intolerance or hypersensitivity to therapy with at least one migraine prophylaxis class OR
    2. The patient has an FDA labeled contraindication to ALL migraine prophylaxis agents (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan) AND
  3. If the client has a preferred agent, then ONE of the following:
    1. The requested agent is a preferred agent for the requested indication OR
    2. The patient has ONE of the following to a preferred agent for the requested indication:
      1. A trial and inadequate response OR
      2. An intolerance or hypersensitivity OR
    3. The patient has an FDA labeled contraindication to ALL preferred agent(s) for the requested indication AND
  4. Medication overuse headache has been ruled out OR
2. The requested agent is being used for the treatment of episodic cluster headache AND ALL of the following:
  1. The patient has had at least 5 cluster headache attacks AND
  2. The patient has at least two cluster period lasting 7-365 days AND
  3. The patient’s cluster periods are separated by a pain-free remission period of greater than or equal to 3 months AND
  4. ONE of the following:
    1. The patient has ONE of the following to at least one prerequisite agent (verapamil, melatonin, corticosteroids, topiramate, OR lithium):
      1. A trial and inadequate response OR
      2. An intolerance or hypersensitivity OR
    2. The patient has an FDA labeled contraindication to ALL prerequisite agents (verapamil, melatonin, corticosteroid, topiramate, AND lithium) AND
  5. Medication overuse headache has been ruled out AND
  6. The requested agent and strength are FDA labeled for episodic cluster headache treatment OR
3. The requested agent is being used for acute migraine treatment AND ALL of the following:
  1. ONE of the following:
    1. The patient has ONE of the following to at least one triptan agent
      1. A trial and inadequate response OR
      2. An intolerance or hypersensitivity OR
    2. The patient has an FDA labeled contraindication to ALL triptan agents AND
  2. The patient will NOT be using the requested agent in combination with another acute migraine therapy (i.e., 5HT-1F, acute use CGRP, ergotamine, triptan) AND
  3. If the client has a preferred agent, then ONE of the following:
    1. The requested agent is a preferred agent for the requested indication OR
    2. The patient has ONE of the following to a preferred agent for the requested indication:
      1. A trial and inadequate response OR
      2. An intolerance or hypersensitivity OR
    3. The patient has an FDA labeled contraindication to ALL preferred agent(s) for the requested indication AND
  4. Medication overuse headache has been ruled out AND
  5. The requested agent and strength are FDA labeled for acute migraine treatment OR
4. The patient has another FDA labeled indication for the requested agent and route of administration OR
5. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
If the patient has an FDA labeled indication, then ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. There is support for using the requested agent for the patient’s age for the requested indication AND
The patient does not have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: Cluster headache treatment - 6 months; migraine prophylaxis - 6 months; all other indications - 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

The patient has been approved for the requested agent previously through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
ONE of the following:
1. BOTH of the following:
  1. ONE of the following:
    1. The requested agent is being used for migraine prophylaxis AND ALL of the following:
      1. The patient has had improvement in migraine prevention (e.g., reduced migraine headache days, reduced migraine frequency, reduced use of acute abortive migraine medication) with the requested agent AND
      2. The patient will NOT be using the requested agent in combination with another prophylactic use CGRP for the requested indication AND
      3. ONE of the following:
        
        BOTH of the following:
        
        The patient has at least 15 headache days per month (chronic migraine) AND
        
        The requested agent and strength are FDA labeled for chronic migraine OR
        
        BOTH of the following:
        
        The patient has less than 15 headache days per month (episodic migraine) AND
        
        The requested agent and strength are FDA labeled for episodic migraine OR
    2. The requested agent is being used for episodic cluster headache treatment AND BOTH of the following:
      1. The patient has had improvement in cluster headaches management with the requested agent AND
      2. The requested agent and strength are FDA labeled for episodic cluster headache treatment OR
    3. The requested agent is being used for acute migraine treatment AND ALL of the following:
      1. The patient has had improvement in acute migraine management with the requested agent AND
      2. The patient will NOT be using the requested agent in combination with another acute migraine therapy (i.e., 5HT-1F, acute use CGRP, ergotamine, triptan) for the requested indication AND
      3. The requested agent and strength are FDA labeled for acute migraine treatment OR
  2. Medication overuse headache has been ruled out OR
2. The requested agent is being used for an indication other than migraine prophylaxis, episodic cluster headache treatment, or acute migraine treatment AND has had clinical benefit with the requested agent AND
The patient does not have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
QL with PA	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the limit OR ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND If the requested agent is being used for treatment of acute migraine, the patient has greater than 4 migraine headaches per month AND ONE of the following: The patient is currently being treated with a migraine prophylactic medication (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], onabotulinum toxin A [Botox]) OR The patient has an intolerance or hypersensitivity to therapy with migraine prophylactic medication [i.e., anticonvulsants (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], OR onabotulinum toxin A [Botox]) OR The patient has an FDA labeled contraindication to ALL migraine prophylactic medications [i.e., anticonvulsants (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], AND onabotulinum toxin A [Botox]) OR There is support that the patient’s migraine is manageable with acute therapy alone AND There is support of therapy with a higher dose for the requested indication Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence Length of Approval: Initial: For migraine prophylaxis: up to 6 months. NOTE: For agents that require a loading dose for a new start, approve the loading dose based on FDA labeling AND the maintenance dose for the remainder of the 6 months. For cluster headache treatment: up to 6 months All other indications: up to 12 months Renewal: up to 12 months

Module

Clinical Criteria for Approval

QL with PA

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
ALL of the following:
1. The requested quantity (dose) exceeds the program quantity limit AND
2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the limit OR
ALL of the following:
1. The requested quantity (dose) exceeds the program quantity limit AND
2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
3. If the requested agent is being used for treatment of acute migraine, the patient has greater than 4 migraine headaches per month AND ONE of the following:
  1. The patient is currently being treated with a migraine prophylactic medication (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], onabotulinum toxin A [Botox]) OR
  2. The patient has an intolerance or hypersensitivity to therapy with migraine prophylactic medication [i.e., anticonvulsants (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], OR onabotulinum toxin A [Botox]) OR
  3. The patient has an FDA labeled contraindication to ALL migraine prophylactic medications [i.e., anticonvulsants (i.e., anticonvulsants [i.e., divalproex, valproate, topiramate], beta blockers [i.e., atenolol, metoprolol, nadolol, propranolol, timolol], antidepressants [i.e., amitriptyline, venlafaxine], candesartan, prophylactic use CGRP [e.g., Aimovig, AJOVY, Emgality, Nurtec, QULIPTA, Vyepti], AND onabotulinum toxin A [Botox]) OR
  4. There is support that the patient’s migraine is manageable with acute therapy alone AND
4. There is support of therapy with a higher dose for the requested indication

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval:

Initial:

For migraine prophylaxis: up to 6 months. NOTE: For agents that require a loading dose for a new start, approve the loading dose based on FDA labeling AND the maintenance dose for the remainder of the 6 months.

For cluster headache treatment: up to 6 months

All other indications: up to 12 months

Renewal: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.