AJOVY, Fremanezumab-vfrm Form

Fremanezumab-vfrm (Ajovy®) is a calcitonin gene-related peptide (CGRP) receptor antagonist. FDA Approved Indication(s) Ajovy is indicated for the preventive treatment of migraine in adults. Policy/Criteria It is the policy of health plans affiliated with Centene Corporation® that Ajovy is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Migraine Prophylaxis (must meet all):

1. Diagnosis of episodic or chronic migraine;
   2. Provider’s attestation that member experiences ≥ 4 migraine days per month for at least 3 months;
   3. Age ≥ 18 years;
   4. Failure of at least 2 of the following oral migraine preventative therapies, each for 8 weeks and from different therapeutic classes, unless clinically significant adverse effects are experienced or all are contraindicated: antiepileptic drugs (e.g., divalproex sodium, sodium valproate, topiramate), beta-blockers (e.g., metoprolol, propranolol, timolol), antidepressants (e.g., amitriptyline, venlafaxine);
2. Failure of Aimovig® and Emgality®, unless clinically significant adverse effects are experienced or both are contraindicated; *Prior authorization may be required.

3. If currently receiving treatment with Botox® for migraine prophylaxis and request is for concurrent use of Botox and Ajovy (i.e., not switching from one agent to another), all of the following (a, b, and c): a. Sufficient evidence is provided from at least two high-quality, published studies in reputable peer-reviewed journals or evidence-based clinical practice guidelines that provide all of the following (i – iv): Case studies or chart reviews are not considered high-quality evidence i. Adequate representation of the member’s clinical characteristics, age, and diagnosis;
   ii. Adequate representation of the prescribed drug regimen;
   iii. Clinically meaningful outcomes such as a reduction in monthly migraine or headache days; iv. Appropriate experimental design and method to address research questions (see Appendix E for additional information); Page 1 of 7

   CLINICAL POLICY Fremanezumab-vfrm b. Member has experienced and maintained positive response to Botox monotherapy as evidenced by a ≥ 30% reduction in migraine days per month from baseline following at least 2 quarterly injection (6 months) of Botox monotherapy; c. Despite Botox monotherapy, member continues to experience ≥ 4 migraine days per month and/or severe migraine headaches that result in disability and functional impairment;

4. Ajovy is not prescribed concurrently with other injectable or oral CGRP inhibitors (e.g., Aimovig™, Emgality®, Vyepti™, Nurtec®, Qulipta™, Ubrelvy™);
5. Dose does not exceed one of the following (a or b): a. 225 mg (1 injection) once monthly; b. 675 mg (3 injections) every 3 months. Approval duration:
   3 months for monthly dosing frequency 6 months for every 3 month dosing frequency B. Other diagnoses/indications (must meet 1 or 2):
6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or
7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace.
   II. Continued Therapy A. Migraine Prophylaxis (must meet all):
8. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
9. Member has experienced and maintained positive response to therapy as evidenced by provider’s attestation of a reduction in migraine days per month from baseline;
   
   3. Ajovy is not prescribed concurrently with other injectable or oral CGRP inhibitors (e.g., Aimovig, Emgality, Vyepti, Nurtec, Qulipta, Ubrelvy);

10. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. 225 mg (1 injection) once monthly; b. 675 mg (3 injections) every 3 months. Page 2 of 7

    CLINICAL POLICY Fremanezumab-vfrm Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):

11. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace; or

12. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – HIM.PA.154 for health insurance marketplace or evidence of coverage documents; B. Cluster headaches.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CGRP: calcitonin gene-related peptide
    FDA: Food and Drug Administration ICHD: International Classification of Headache Disorder Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Anticonvulsants such as: divalproex (Depakote®), topiramate (Topamax®), valproate sodium Beta-blockers such as: propranolol (Inderal®), metoprolol (Lopressor®), timolol, atenolol (Tenormin®), nadolol (Corgard®)*
    Migraine Prophylaxis Refer to prescribing information or Micromedex Dose Limit/ Maximum Dose Refer to prescribing information or Micromedex Migraine Prophylaxis Refer to prescribing information or Micromedex Refer to prescribing information or Micromedex Page 3 of 7

    CLINICAL POLICY Fremanezumab-vfrm Drug Name Dosing Regimen Antidepressants/tricyclic antidepressants such as: amitriptyline (Elavil®), venlafaxine (Effexor®) Aimovig® (erenumab-aaoe) Migraine Prophylaxis Refer to prescribing information or Micromedex Dose Limit/ Maximum Dose Refer to prescribing information or Micromedex Migraine Prophylaxis
    70 mg SC once monthly 140 mg/month Some patients may benefit from a dosage of 140 mg injected subcutaneously once monthly Emgality® (galcanezumab-gnlm) Migraine Prophylaxis
    120 mg/month Loading dose: 240 mg SC once Maintenance dose: 120 mg SC once monthly Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Off-label use Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity • Boxed warning(s): none reported Appendix D: General Information
    • In clinical trials, a migraine day was defined as any calendar day in which the patient reported either a headache that lasted at least 2 consecutive hours and met International Classification of Headache Disorder (ICHD)-3 diagnostic criteria for migraine (with or without aura) or probable migraine (subtype in which only 1 migraine criterion is absent), or a day when a headache of any duration was treated with migraine-specific medications (triptans or ergots).
    • The ENFORCE Phase III clinical trial program evaluating the efficacy of Ajovy in episodic and chronic cluster headache was discontinued after a pre-specified futility analysis revealed that the study’s primary endpoints were unlikely to be met. Appendix E: Appropriate Experimental Design Methods • Randomized, prospective controlled trials are generally considered the gold standard; however:
    o In some clinical studies, it may be unnecessary or not feasible to use randomization, double-blind trials, placebos, or crossover. o Non-randomized prospective clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of drugs. Page 4 of 7

    CLINICAL POLICY Fremanezumab-vfrm • Case reports and chart reviews are generally considered uncontrolled and anecdotal information and do not provide adequate supportive clinical evidence for determining accepted uses of drugs.
    V. Dosage and Administration
    Indication Migraine prophylaxis Dosing Regimen 225 mg SC once monthly or 675 mg SC every three months Maximum Dose 675 mg every 3 months VI. Product Availability
    Single-dose prefilled syringe, autoinjector: 225 mg/1.5 mL VII.