Oscar Anti-migraine Agents/ Calcitonin Gene-Related Peptide (CGRP) Antagonists and Serotonin Receptor 5-HT1F Agonists (PG008) Form

Migraines are pulsating headaches with intense, throbbing pain that can last from hours to days. It can affect one or both sides of the head, and is commonly associated with other symptoms such as sensitivity to light and/or noise, 1 pressure behind the eye(s), nausea, and vomiting. Along with lifestyle changes, migraine headaches can be treated with medicines that relieve pain, nausea, or that prevent migraine headaches from happening. Starting in 2018, a new class of drugs called anti-calcitonin gene-related peptide (anti-CGRP) antibodies became available, allowing for new treatment options (acute treatment or prophylactic) for migraine headaches. There are some CGRP antagonists FDA indicated for use in migraine prevention, while others are FDA indicated for use in migraine treatment. The CGRP antagonists indicated for migraine prevention include Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Nurtec ODT (rimegepant), and Vyepti (eptinezumab). ● Aimovig, Ajovy, and Emgality are available as a subcutaneous (SC) formulation. ● Nurtec ODT (rimegepant) and Qulipta (atogepant) are available in oral formulation. ● Vyepti (IV) is available as an intravenous formulation. The CGRP antagonists indicated for migraine treatment include Nurtec ODT (rimegepant), Zavzpret (zavegepant), and Ubrelvy (ubrogepant). Reyvow, a serotonin receptor 5-HT1F agonist, is also used for the acute treatment of migraines. ● Nurtec and Ubrelvy are available as an oral formulation. ● Reyvow is available in an oral tablet formulation. ● Zavzpret is available as a nasal spray. Table 1: Calcitonin Gene-Related Peptide (CGRP) Antagonists and Serotonin Receptor 5-HT1F Agonists Drug FDA-Approved Indications Classification Formulary Agents Aimovig (erenumab) Ajovy (fremanezumab) Emgality (galcanezumab) Nurtec ODT (rimegepant) is indicated for the preventive treatment of migraine in adults. is indicated for the preventive treatment of migraine in adults. is indicated for: ● ● the preventive treatment of migraine in adults. for the treatment of episodic cluster headache in adults. Calcitonin Gene- Related Peptide (CGRP) Antagonists is indicated for: ● ● the acute treatment of migraine with or without aura in adults . the preventive treatment of episodic migraine in adults. Non-Formulary Agents 2 Qulipta (atogepant) is indicated for the preventive treatment of migraine in adults. Ubrelvy (ubrogepant) is indicated for the acute treatment of migraine with or without aura in adults. Vyepti (eptinezumab) is indicated for the preventive treatment of migraine in adults. Calcitonin Gene- Related Peptide (CGRP) Antagonists Zavzpret (zavegepant) is indicated for the acute treatment of migraine with or without aura in adults. Reyvow (lasmiditan) is indicated for the acute treatment of migraine with or without aura in adults. Selective Serotonin 1F Receptor (5-HT1F) Agonists (Ditans) NOTE: The Plan requires that members be unable to use, or have tried and failed preferred medication(s) first. Requests for non-formulary medications are also subject to Medical Necessity Criteria for Non-Formulary Drugs (PG069). Definitions “Cluster headache” is a primary headache disorder as defined by the International Classification of Headache Disorders that is associated with intense pain that often occurs in or around one eye or on one side of a person’s head. Attacks often suddenly in the middle of the night in a cyclical pattern lasting for weeks or months. Common symptoms experienced during a cluster headache episode include restlessness/agitation, increased redness, swelling, or tearing of the eye, stuffy or runny nose, eyelid drooping, or facial sweating and flushing. “Chronic cluster headache” refers to a series of cluster headache attacks occurring for one year or longer without remission or with remission periods lasting less than 3 months. “Episodic cluster headache” refers to a series of cluster headache attacks occurring in periods lasting from 7 days to one year, separated by pain-free periods of 3 or more months. “Migraine” is a primary headache disorder with diagnostic criteria defined by the International Classification of Headache Disorders that is associated with four distinct stages: prodrome, aura, attack and post-drome. However, everyone who has migraines does not experience all four stages. There are two major types of migraines: 1) migraine without aura and 2) migraine with aura. 3 “Aura” is a set of reversible symptoms that occur before or during a migraine episode. Examples of conditions associated with migraine aura include vision loss or sudden changes (such as seeing shapes, bright spots or flashes of light), hearing noises or music, tingling sensation in arms or legs, numbness of the face or side of the body, or difficulty speaking. “Chronic migraine” is characterized by 15 or more headache days per month for 3 or more months. “Episodic migraine” is characterized by 0 to 14 headache days per month. Medical Necessity Criteria for Authorization The Plan considers Anti-migraine Agents medically necessary when ALL the following criteria are met for the applicable indication listed below: Products for use in Migraine Prophylaxis (Prevention): Medical Necessity Criteria for Initial Authorization The Plan considers Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Nurtec ODT (rimegepant), Qulipta (atogepant), and Vyepti (eptinezumab) medically necessary for migraine prophylaxis when ALL of the following criteria are met: 1. The member is 18 years of age or older; AND 2. The member has a diagnosis of migraine (with or without aura) according to the International Classification of Headache Disorders (see Appendix, Table 2); AND 3. The member experiences four (4) or more migraine days per month; AND 4. The member is unable to use, or adequately tried and failed an 8-week trial of at least two (2) preventative therapies, from at least two (2) of the following drug classes: a. Anticonvulsants (e.g., topiramate, divalproex, sodium valproate); or b. Antidepressants (e.g., amitriptyline, nortriptyline, venlafaxine); or c. Beta blockers (e.g., propranolol, metoprolol); AND 5. The requested medication will not be used concomitantly with: a. Botulinum toxin (e.g. Botox, Dysport); or b. another CGRP antagonist for migraine prophylaxis; AND 6. Chart documentation substantiating the above criteria is provided for review. If the above prior authorization criteria is met, the requested medication will be approved for 6 months. 4 Medical Necessity Criteria for Reauthorization Reauthorization for 12 months will be granted if the member has clinical chart documentation confirming BOTH of the following criteria: 1. The member has experienced meaningful clinical improvement in frequency and/or severity of migraine episodes; AND 2. The requested medication will not be used concomitantly with: a. Botulinum toxin (e.g. Botox, Dysport); or b. another CGRP antagonist for migraine headache prophylaxis. Products for use as Acute Headache Therapies For use in the treatment of Acute Migraine: Medical Necessity Criteria for Initial Authorization The Plan considers Nurtec ODT (rimegepant), Reyvow (lasmiditan), Ubrelvy (ubrogepant), and Zavzpret (zavegepant) medically necessary for the acute treatment of migraine when ALL of the following criteria are met: 1. The member is 18 years of age or older; AND 2. The member has a diagnosis of migraine (with or without aura) according to the International Classification of Headache Disorders (see Appendix, Table 2); AND 3. The member is unable to use, or has tried and failed two (2) different triptan agents (e.g., as sumatriptan, eletriptan, naratriptan); AND 4. The requested medication will not be used concomitantly with another CGRP antagonist for acute/abortive migraine treatment; AND 5. Chart documentation substantiating the above criteria is provided for review. If the above prior authorization criteria is met, the requested medication will be approved for 6 months. Medical Necessity Criteria for Reauthorization Reauthorization for 12 months will be granted if the member has clinical chart documentation confirming BOTH of the following criteria: 1. The member has experienced meaningful clinical improvement in frequency and/or severity of migraine episodes; AND 2. The requested medication will not be used concomitantly with another CGRP antagonist for acute/abortive treatment. 5 For use in the treatment of Episodic Cluster Headache: Medical Necessity Criteria for Initial Authorization The Plan considers Emgality (galcanezumab) medically necessary for the treatment of episodic cluster headache when ALL of the following criteria are met: 1. The member is 18 years of age or older; AND 2. The member has a diagnosis of episodic cluster headache according to the International Classification of Headache Disorders (see Appendix, Table 2); AND 3. The member is unable to use, or has tried and failed verapamil; AND 4. The requested medication will not be used concomitantly with another CGRP antagonist for acute/abortive cluster headache treatment; AND 5. Chart documentation substantiating the above criteria is provided. If the above prior authorization criteria is met, the requested medication will be approved for 6 months. Medical Necessity Criteria for Reauthorization Reauthorization for 12 months will be granted if the member has clinical chart documentation confirming BOTH of the following criteria: 1. The member has experienced meaningful clinical improvement in frequency and/or severity of cluster headache episodes; AND 2. The requested medication will not be used concomitantly with another CGRP antagonist for acute/abortive cluster headache treatment. Experimental or Investigational / Not Medically Necessary CGRP Antagonists for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven. Appendix Table 2: Diagnostic criteria according to the International Classification of Headache Disorders, 3rd edition Diagnosis Criteria Migraine without aura BOTH of the following: (ICHD-3) 1. A history of at least 5 attacks1 meeting ALL of the following: a. Migraine headache lasting at least 4 hours2,3; and 6 b. Migraine headache is characterized by at least TWO of the following: and i. Aggravation by or causing avoidance of routine physical activity; or ii. Moderate to severe pain; or iii. iv. Pulsating quality; or Unilateral (one-sided) location; and c. During headache, at least ONE of the following: i. Nausea and/or vomiting; or ii. Photophobia (sensitivity to light) and/or phonophobia (sensitivity to sound); and 2. Provider attestation indicating that other potential causes of headache have been ruled out Migraine with aura BOTH of the following: 1. A history of at least 2 attacks meeting BOTH of the following: a. At least ONE of the following fully reversible aura symptoms: i. Brainstem (e.g., dysarthria, vertigo, tinnitus, diplopia); or ii. Motor; or iii. iv. v. vi. Retinal (eg, scintillations, scotomata, blindness); or Sensory, including positive features (e.g., pins and needles) and/or negative features (e.g., numbness); or Speech and/or language (e.g., loss of ability to express speech); or Visual, including positive features (e.g., flickering lights, spots, lines) and/or negative features (e.g., loss of vision); and b. At least three of the following: i. ii. iii. iv. v. vi. At least one aura symptom is positive6; or At least one aura symptom is unilateral5; or At least one aura symptoms spreads gradually over 5 or more minutes; or Each individual aura symptom lasts between 5 and 60 minutes4; or The aura is accompanied or followed within 60 minutes by headache; or Two or more symptoms occur in succession; and 7 Episodic Cluster Headache 2. Provider attestation indicating that other potential causes of headache have been ruled out ALL of the following: 1. A history of at least 5 attacks meeting ALL of the following: a. of severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes7; and b. occurring with a frequency between one every other day and eight per day8; and c. Headache is accompanied by a sense of restlessness or agitation and/or at least one of the following (on the same side of the body): i. ii. iii. iv. v. Eyelid swelling or drooping; or Increased redness or tearing of the eye; or Forehead and facial sweating; or Pupil contraction; or Stuffy or runny nose; and 2. The member has at least two cluster periods lasting one week to a year, separated by attack-free intervals (i.e. remission) lasting at least 3 months; and 3. Provider attestation indicating that other potential causes of headache have been ruled out 1 Distinguishing a single migraine attack from a symptomatic migraine-like attack can be challenging. Additionally, the nature of only one or a few attacks may be difficult to ascertain. Therefore, a diagnosis of migraine without aura requires at least five attacks to establish the disease pattern. Patients with fewer than five attacks who otherwise meet diagnostic criteria should be designated as having probable migraine without aura. 2 If a migraine attack ends when the patient falls asleep, the duration of the attack should be determined based on the time up until the point of falling asleep. 3 In children and adolescents under 18 years of age, migraine attacks may last from 2 hours up to 72 hours. Evidence has not confirmed untreated attack durations of less than 2 hours in pediatric patients. 4 If three distinct aura symptoms occur, the maximum acceptable total duration would be 3 × 60 minutes. Motor symptoms may persist for up to 72 hours. 5 Aphasia should always be categorized as a unilateral symptom. Dysarthria may or may not be unilateral. 6 Positive aura symptoms include scintillations and pins and needles sensations. 7 For less than half of the duration of an active cluster headache period, some attacks may be of lesser severity and/or shorter or longer duration compared to a patient's typical attack pattern. 8 For less than half of the duration of an active cluster headache period, some attacks may occur at a lower frequency than is typical for a patient. 8 Table 3: ICD-10-CM (diagnosis) Codes for Migraine and Cluster Headaches Codes Description G43.0 Migraine without aura (common migraine) G43.001 Migraine without aura, not intractable, with status migrainosus G43.009 Migraine without aura, not intractable, without status migrainosus G43.011 Migraine without aura, intractable, with status migrainosus G43.019 Migraine without aura, intractable, without status migrainosus G43.1 Migraine with aura (classical migraine) G43.101 Migraine with aura, not intractable, with status migrainosus G43.109 Migraine with aura, not intractable, without status migrainosus G43.111 Migraine with aura, intractable, with status migrainosus G43.119 Migraine with aura, intractable, without status migrainosus G43.2 G43.3 Status migrainosus Complicated migraine G43.701 Chronic migraine without aura, not intractable, with status migrainosus G43.709 Chronic migraine without aura, not intractable, without status migrainosus G43.711 Chronic migraine without aura, intractable, with status migrainosus G43.719 Chronic migraine without aura, intractable, without status migrainosus G43.801 Other migraine, not intractable, with status migrainosus G43.809 Other migraine, not intractable, without status migrainosus G43.811 Other migraine, intractable, with status migrainosus G43.819 Other migraine, intractable, without status migrainosus G43.901 Migraine, unspecified, not intractable, with status migrainosus G43.909 Migraine, unspecified, not intractable, without status migrainosus G43.911 Migraine, unspecified, intractable, with status migrainosus G43.919 Migraine, unspecified, intractable, without status migrainosus G44.001 Cluster headache syndrome, unspecified, intractable G44.009 Cluster headache syndrome, unspecified, not intractable G44.011 Episodic cluster headache, intractable 9 G44.019 Episodic cluster headache, not intractable G44.021 Chronic cluster headache, intractable Chronic cluster headache, not intractable G44.029 References 1. 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New York, NY: Pfizer Labs; March 2023. 11 Clinical Guideline Revision / History Information Original Date: 08/06/2020 Reviewed/Revised: 06/24/2021, 12/01/2021, 06/23/2022, 9/15/2022, 12/14/2023 12