Coverage Policy Manual
Policy #: 2020007
Category: Pharmacy
Initiated: April 2020
Last Review: December 2024
  Eptinezumab-jjmr (e.g., VYEPTI)
Description:
Eptinezumab-jjmr is a humanized monoclonal antibody that selectively blocks both alpha- and beta-  calcitonin gene-related peptides (CGRP). Eptinezumab-jjmr is indicated for the preventive treatment of migraine in adults.
 
Regulatory Status
 
Eptinezumab-jjmr (e.g., VYEPTI) was approved by the U.S. Food and Drug Administration (FDA) on February 21, 2020 as a preventative treatment of migraine in adults.
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Effective April 01, 2022 Prior Approval is required for Eptinezumab-jjmr (e.g., Vyepti).  
 
Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective July 9, 2025
  
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
  
Eptinezumab-jjmr (e.g., Vyepti) meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:
 
For FDA labeled indications, Eptinezumab-jjmr (e.g., Vyepti) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified in the dosage and administration section.  
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
  
1. Individual is 18 years of age or older; (Vyepti, 2020); AND
2. Prescribed by or in consultation with a neurologist; AND
3. Individual has a diagnosis of:
a. Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; OR
b. Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; (Vyepti, 2020); AND
4. Individual experiences 4 or more migraine days per month (Vyepti, 2020); AND
5. Individual has had an inadequate treatment response with an 8-week trial of two of the following medications from different pharmacological classes:
a. Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol (Silberstin, 2012);
b. Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012);
c. Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012);
d. Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012);
e. Botulinum toxin (for chronic migraine, AAN 2016); AND
6. Individual must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g., Emgality, Aimovig) (AAN 2016); AND
7. If request is for dose 300 mg, individual has completed at least 3 doses of 100 mg with partial or inadequate response.  
  
CONTINUED APPROVAL for up to 12 months:
 
1. Individual demonstrates clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency); AND
2. Individual is NOT taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g., Emgality, Aimovig) (AAN 2016).
  
Dosage and Administration  
Dosing per FDA Guidelines unless otherwise specified below.  
 
The recommended dose of eptinezumab-jjmr (e.g., Vyepti) is 100 mg or 300 mg.
 
Eptinezumab-jjmr (e.g., Vyepti) should be administered by intravenous infusion over approximately 30 minutes every 3 months by a healthcare professional.
  
Eptinezumab-jjmr (e.g., Vyepti) is available as a 100mg solution in a single-dose vial.
  
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
  
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
  
Eptinezumab-jjmr (e.g., Vyepti) for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, Eptinezumab-jjmr (e.g., Vyepti) for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective December 2023 to July 8, 2025
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
 
    1. Individual is 18 years of age or older; (FDA, Vyepti, 2020) AND
    2. Prescribed by or in consultation with a neurologist AND  
    3. Individual has a diagnosis of:
a.  Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; OR
b.  Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
4.  Individual experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
5.  Individual has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
a.  Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol (Silberstin, 2012);
b.  Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
c.  Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
d.  Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
e.  Botulinum toxin (for chronic migraine, AAN 2016); AND
6.  Individual must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g., Emgality, Aimovig) (AAN 2016); AND
7.  Individual is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (Baker, 2020); AND
8. Must be dosed in accordance with the FDA label.
 
CONTINUATION OF THERAPY for 12 months:
 
1.   Must demonstrate clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency.)  AND
2.  Must not be taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g., Emgality, Aimovig) (AAN 2016)
 
Dosage and Administration
Dosing per FDA Guidelines
 
Eptinezumab-jjmr is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eptinezumab-jjmr for any indication or circumstance not described above, including but not limited to, dosage above 100 mg once every 3 months (Baker, 2020), does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr for any indication or circumstance not described above, including but not limited to, dosage above 100 mg once every 3 months (Baker, 2020), is considered not medically necessary. Not medically necessary services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective August 16, 2023 to November 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr meets primary coverage criteria that there be scientific evidence for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Individual is 18 years of age or older; (FDA, Vyepti, 2020) AND
    2. Prescribed by or in consultation with a neurologist AND  
    3. Individual has a diagnosis of:
a.  Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; or
b.  Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
4.  Individual experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
5.  Individual has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
a.  Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol; (Silberstin, 2012)
b.  Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
c.  Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
d.  Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
e.  Botulinum toxin (for chronic migraine, AAN 2016)
6.  Individual must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig).; (AAN 2016) AND
7.  Individual is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (Baker, 2020)
 
CONTINUATION OF THERAPY for 12 months:
1.   Must demonstrate clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency.)  AND
2.  Must not be taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig). (AAN 2016)
 
Dosage and Administration
 
Eptinezumab-jjmr is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Eptinezumab-jjmr for any indication or circumstance not described above, including but not limited to, dosage above 100 mg once every 3 months (Baker, 2020), does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr for any indication or circumstance not described above, including but not limited to, dosage above 100 mg once every 3 months (Baker, 2020), is considered not medically necessary. Not medically necessary services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective July 12, 2023 to August 15, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr meets primary coverage criteria that there be scientific evidence for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Member is 18 years of age or older; (FDA, Vyepti, 2020) AND
    2. Prescribed by or in consultation with a neurologist AND  
    3. Member has a diagnosis of:
a.  Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; or
b.  Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
4.  Member experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
5.  Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
a.  Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol; (Silberstin, 2012)
b.  Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
c.  Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
d.  Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
e.  Botulinum toxin (for chronic migraine, AAN 2016)
6.  Member must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig).; (AAN 2016) AND
7.  Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (Baker, 2020)
 
CONTINUATION OF THERAPY for 12 months:
1.   Must demonstrate clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency.)  AND
2.  Must not be taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig). (AAN 2016)
 
Dosage and Administration
 
Eptinezumab-jjmr is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 22, 2023 to July 11, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr meets primary coverage criteria that there be scientific evidence for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Member is 18 years of age or older; (FDA, Vyepti, 2020) AND
    2. Prescribed by or in consultation with a neurologist AND  
    3. Member has a diagnosis of:
a.  Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; or
b.  Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
4.  Member experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
5.  Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
a.  Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol; (Silberstin, 2012)
b.  Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
c.  Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
d.  Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
e.  Botulinum toxin (for chronic migraine, AAN 2016)
6.  Member must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig).; (AAN 2016) AND
7.  Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (Baker, 2020)
 
CONTINUATION OF THERAPY for 12 months:
1.   Must demonstrate clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency.)  AND
2.  Must not be taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig). (AAN 2016)
 
Dosage and Administration
Dosing per FDA Guidelines
 
Eptinezumab-jjmr is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 1, 2022 to March 21, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr meets primary coverage criteria that there be scientific evidence for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
    1. Member is 18 years of age or older; (FDA, Vyepti, 2020) AND
    2. Prescribed by or in consultation with a neurologist AND  
    3. Member has a diagnosis of:
a.  Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; or
b.  Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
4.  Member experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
5.  Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
a.  Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol; (Silberstin, 2012)
b.  Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
c.  Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
d.  Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
e.  Botulinum toxin (for chronic migraine, AAN 2016)
6.  Member must not be taking concurrently with botulinum or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig).; (AAN 2016) AND
7.  Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (FDA, Vyepti, 2020)
8.  Must be dosed in accordance with the FDA label.
 
CONTINUATION OF THERAPY for 12 months:
1.   Must demonstrate clinical improvement in frequency and symptoms of migraine (i.e., frequency of abortive use and documented headache frequency.)  AND
2.  Must not be taking concurrently with botulinum, or any other preventive CGRP inhibitor (e.g.,Emgality, Aimovig). (AAN 2016)
 
Dosage and Administration
Dosing per FDA Guidelines
 
Eptinezumab-jjmr is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
EFFECTIVE JANUARY 2022 to March 31, 2022
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) meets primary coverage criteria that there be scientific evidence for the prophylaxis treatment of migraine in adults when ALL the following criteria are met:
 
      1. Member is 18 years of age or older; (FDA, Vyepti, 2020) AND
      2. Prescribed by or in consultation with a neurologist AND  
      3. Member has a diagnosis of:
          1. Chronic migraines [as a headache occurring on 15 or more days per month for more than 3 months, which, on at least 8 days per month, has features of a migraine headache (ICHD-3)]; or
          2. Episodic migraines [at least 4 and fewer than 15 migraine days per month and fewer than 15 headache days per month on average during the previous 3-month period]; ( (FDA, Vyepti, 2020); AND
      4. Member experiences 4 or more migraine days per month (FDA, Vyepti, 2020) AND  
      5. Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
          1. Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, nadolol; (Silberstin, 2012)
          2. Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium; (Silberstin, 2012)
          3. Antidepressant agents: Amitriptyline or Venlafaxine; (Silberstin, 2012)
          4. Angiotensin receptor blocking agent: Candesartan. (Silberstin, 2012)
          5. Botulinum toxin (for chronic migraine, AAN 2016)
      6. Member must not be taking concurrently with botulinum toxin, Erenumab (AIMOVIGTM), Fremanezumab (AJOVYTM), or Galcanezumab (EMGALITYTM); (AAN 2016) AND
      7. Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months. (FDA, Vyepti, 2020)
 
For continuation of Eptinezumab-jjmr, the member:
      1. Must demonstrate clinical improvement in frequency and symptoms of migraine AND
      2. Must not be taking concurrently with botulinum, Erenumab (AIMOVIGTM), Fremanezumab (AJOVYTM), or Glacanezumab (EMGALITYTM). (AAN 2016)
 
Dosage and Administration
 
Eptinezumab-jjmr (VYEPTI™) is administered by intravenous infusion over approximately 30 minutes every 3 months.
Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) does not meet member benefit certificate primary coverage criteria that there be scientific evidence for any other indication.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective November 2021- December 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) meets primary coverage criteria that there be scientific evidence for the preventive treatment of migraine in adults when the following criteria are met:
 
      1. Member is 18 years of age or older AND
      2. Prescribed by or in consultation with a neurologist AND  
      3. Member has a diagnosis of chronic or episodic migraines AND
      4. Member experiences 4 or more migraine days per month AND  
      5. Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
          1. Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, or Nadolol
          2. Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium
          3. Antidepressant agents: Amitriptyline or Venlafaxine
          4. Angiotensin receptor blocking agent: Candesartan
 
AND
 
6. Member has had an inadequate treatment response with any one of the following:
          1. Botulinum toxin
          2. Erenumab
          3. Fremanezumab
          4. Galcanezumab
 
AND
 
7. Member must not be taking concurrently with Erenumab (AIMOVIGTM), Fremanezumab (AJOVYTM), Galcanezumab (EMGALITYTM), or botulinum toxin AND
 
8.  Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months
 
Dosage and Administration
 
Eptinezumab-jjmr (VYEPTI™) is administered by intravenous infusion over approximately 30 minutes every 3 months.
Recommended dose is 100mg.
 
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) does not meet member benefit certificate primary coverage criteria that there be scientific evidence for any other indication.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage..
 
Effective December 2020- October 2021
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) meets primary coverage criteria that there be scientific evidence for the preventive treatment of migraine in adults when the following criteria are met:
    1. Member is 18 years of age or older AND
    2. Prescribed by or in consultation with a neurologist or headache specialist AND  
    3. Member has a diagnosis of chronic or episodic migraines AND
    4. Member experiences 4 or more migraine days per month AND  
    5. Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
        1. Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, or Nadolol
        2. Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium
        3. Antidepressant agents: Amitriptyline or Venlafaxine
        4. Angiotensin receptor blocking agent: Candesartan
 AND
6. Member has had an inadequate treatment response with any one of the following:
        1. Botulinum toxin
        2. Erenumab
        3. Fremanezumab
        4. Galcanezumab
 AND
7. Member must not be taking concurrently with Erenumab (AIMOVIGTM), Fremanezumab (AJOVYTM), Galcanezumab (EMGALITYTM), or botulinum toxin AND
8. Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months
 
Dosage and Administration
 
Eptinezumab-jjmr (VYEPTI™) is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) does not meet member benefit certificate primary coverage criteria that there be scientific evidence for any other indication.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
 
Effective April 2020 to November 2020
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) meets primary coverage criteria for the preventive treatment of migraine in adults when the following criteria are met:
 
    1. Member is 18 years of age or older AND
    2. Prescribed by or in consultation with a neurologist or headache specialist AND  
    3. Member has a diagnosis of chronic or episodic migraines AND
    4. Member experiences 4 or more migraine days per month AND  
    5. Member has had an inadequate treatment response with an 8-week trial of two of the following from different pharmacological classes:
        1. Beta-adrenergic blocking agents: Propranolol, Timolol, Metoprolol, Atenolol, or Nadolol
        2. Antiepileptic agents: Divalproex Sodium, Topiramate, or Valproate Sodium
        3. Antidepressant agents: Amitriptyline or Venlafaxine
        4. Angiotensin receptor blocking agent: Candesartan
 OR
6. Member has had an inadequate treatment response with any one of the following:
        1. Onabotulinumtoxin A
        2. Erenumab
        3. Fremanezumab
        4. Galcanezumab
 AND
7. Member must not be taking with Erenumab (AIMOVIGTM), Fremanezumab (AJOVYTM), or Galcanezumab (EMGALITYTM) AND
8. Member is to receive Eptinezumab-jjmr 100mg by intravenous infusion once every 3 months
 
Dosage and Administration
 
Eptinezumab-jjmr (VYEPTI™) is administered by intravenous infusion over approximately 30 minutes every 3 months. Recommended dose is 100mg.
Eptinezumab-jjmr is available as a 100mg solution in a single-dose vial.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Eptinezumab-jjmr (VYEPTI™) does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, Eptinezumab-jjmr is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
Migraines affect about 12% of adults in the United States and are the second leading cause of disability worldwide. Migraine symptoms interfere with daily life and contribute to the development of comorbidities such as cardiovascular disease, anxiety, and depression. Migraines are classified based on the number of headache days per month. Episodic migraine is described as 0 – 14 headache days per month and represents 90% of migraine patients. Chronic migraine is described as 15 or more headache days per month and represents 10% of migraine patients.
 
The CGRP appears to mediate trigeminovascular pain transmission and the vasodilatory component of neurogenic inflammation. It’s hypothesized that blocking the release of CGRP decreases the occurrence of migraine. There are four CGRP inhibitors available for migraine prophylaxis: Erenumab, Fremanezumab, Galcanezumab, and now Eptinezumab-jjmr. Other therapies available for migraine prophylaxis include beta blockers, calcium channel blockers, antidepressants, antiepileptics, and Onabotulinumtoxin A.
 
The efficacy of Eptinezumab-jjmr was evaluated as a preventive treatment of episodic and chronic migraines two studies: one study in patients with episodic migraine (PROMISE-1) and one study in patients with chronic migraine (PROMISE-2).
 
PROMISE-1 was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults 18-75 years of age with a diagnosis of migraine at or before 50 years of age were eligible for the study. These adults were included in the study if they had a history of migraines for the past 12 months or more and had less than or equal to 14 headache days were month, including 4 or more migraine days, in the 3 months prior to screening. 665 patients were randomized to receive an intravenous infusion of one of the following every 3 months for 12 months: placebo (N=222), 100mg Eptinezumab-jjmr (N=221), or 300mg Eptinezumab-jjmr (N=222). Patients kept an eDiary to record information regarding migraine/headache characteristics, severity, duration, and acute migraine medication use. Patients were allowed to use concurrent acute migraine or headache medications. The primary endpoint was change from baseline in mean monthly migraine days. The secondary endpoints included the percentages of patients with 50% or greater and 75% or greater reductions from baseline in monthly migraine days. The total duration of the study was 60 weeks. The primary and secondary efficacy analyses were based on data at week 12. The mean migraine days per month at baseline was approximately 8.6 and was similar across treatment groups. At week 12 Eptinezumab-jjmr 100mg and 300mg demonstrated statistically significant reduction from baseline in the number of migraine days per month compared with placebo (30mg, -4.0; 100mg, -3.9; 300mg, -4.3; placebo, -3.2). (Ashina M, Saper J, Cady R, et al., 2020)
 
PROMISE-2 was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the safety and efficacy of Eptinezumab-jjmr in adult patients diagnosed with chronic migraine. Adults 18-65 years of age with a diagnosis of migraine at or before 50 years of age were eligible for the study. These adults were included in the study if they had a history of chronic migraines for the past 12 months or more, experienced 15 – 26 headache days per month, and 8 or more migraine days per month. 1,072 patients were randomized to receive an intravenous infusion of one of the following every 3 months for 6 months: placebo (N=366), 100mg Eptinezumab-jjmr (N=356), or 300mg Eptinezumab-jjmr (N=350). Patients kept a daily eDiary to report headaches, migraines, and any acute therapies used. Patients were allowed to use concurrent acute migraine or headache medications. The primary endpoint was change from baseline in mean migraine days per month over weeks 1 to 12. The secondary endpoints included the percentage of patients with 50% or greater and 75% or greater reductions from baseline in monthly migraine days over months 1 to 3. The mean migraine days per month at baseline was approximately 16.1 and was similar across treatment groups. At week 12 Eptinezumab-jjmr 100mg and 300mg demonstrated a statistically significant reduction from baseline in number of migraine days per month compared to placebo (100mg, -7.7; 300mg, -8.2; placebo, -5.6). (Lipton RB, Goadsby PJ, Smith J, et al., 2020)
 
The most common adverse reactions in the clinicals trials for both episodic and chronic migraines were nasopharyngitis (100mg, 6%; 300mg, 8%; placebo, 6%) and hypersensitivity (100mg, 1%; 300mg, 2%; placebo, 0%). 1.9% of patients discontinued treatment due to hypersensitivity reactions including angioedema, urticaria, facial flushing, and rash.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
This post hoc subgroup analysis evaluated the efficacy and safety of eptinezumab for migraine prevention in patients with migraine and self-reported aura.
 
PROMISE-1 (NCT02559895; episodic migraine) and PROMISE-2 (NCT02974153; chronic migraine) were randomized, double-blind, placebo-controlled trials that evaluated eptinezumab for migraine prevention. In both studies, the primary outcome was the mean change from baseline in monthly migraine days over Weeks 1-12. Patients in this analysis included those who self-reported migraine with aura at screening.
 
Of patients with episodic migraine, ∼75% reported a history of aura at screening; of patients with chronic migraine, ∼35% reported a history of aura. Changes in monthly migraine days over Weeks 1-12 were -4.0 (100 mg) and -4.2 (300 mg) with eptinezumab versus -3.1 with placebo in patients with episodic migraine with aura and were -7.1 (100 mg) and -7.6 (300 mg) with eptinezumab versus -6.0 with placebo in patients with chronic migraine with aura. Treatment-emergent adverse events were reported by 56.0% (100 mg), 57.4% (300 mg), and 55.4% (placebo) of patients.
 
The preventive migraine efficacy of eptinezumab in patients in the PROMISE studies who self-reported aura was comparable to the overall study populations, demonstrating a similarly favorable safety and tolerability profile. (Ashina M, McAllister P, Cady R, et.al., 2022)
 
August 2023 Update
In the trials that led to approval, doses of both 100 mg and 300 mg every 3 months were compared against placebo. 100 mg and 300 mg doses were not compared against each other, nor were members that did not respond to 100 mg escalated to 300 mg (Ashina, 2020) (Lipton, 2020). A review of population pharmacokinetic and exposure-response of eptinezumab found that “the most important covariates describing the variability of eptinezumab CL were body weight, renal function, disease state (healthy, EM, CM), and baseline MMDs, whereas the most important covariates describing the variability of Vc were body weight, disease, and sex. Although these effects [were] noted, the relatively small changes in CL and Vc [did] not suggest that dosage adjustments are necessary. These findings are in line with other mAbs that inhibit the CGRP biology (i.e., galcanezumab, fremanezumab, erenumab) for which these patient characteristics do not produce clinically meaningful changes in any PK parameters. As eptinezumab doses increased to 100 mg, there was an increased probability of a reduction in the frequency of MMD over weeks 1‐12, with a plateau of effect as the dose was further increased to 300 mg. This similar efficacy between the 100‐mg and 300‐mg doses supports the notion of a lowest effective dose of 100 mg. The results of the exposure‐response analysis for secondary endpoints reinforced the less robust response at the 30‐mg dose level and the presence of a plateau effect between 100 and 300 mg. This suggests that doses of 100 and 300 mg would result in similar efficacy. (Baker, 2020).
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Eptinezumab demonstrated efficacy in adults with migraine and prior preventive treatment failures in the placebo-controlled phase of the DELIVER clinical trial. Evaluation of  the long-term effectiveness of eptinezumab in a migraine patient population was studied during the 48-week extension phase of DELIVER.
 
DELIVER was conducted June 1, 2020 to September 15, 2022. 865 adults with migraine, with documented evidence of 2-4 prior preventive migraine treatment failures and with completion of the 24-week placebo-controlled period of DELIVER received eptinezumab (100 or 300 mg) during the dose-blinded extension, either continuing their randomized dose or, if originally receiving placebo, were randomized 1:1 to an eptinezumab dose (100 or 300 mg). A mixed model for repeated measures was used to evaluate changes from baseline in the number of monthly migraine days (MMDs).
 
Of 865 patients entering the extension (eptinezumab 100 mg, n = 433; 300 mg, n = 432), 782 (90.4%) completed and 11 (1.3%) discontinued due to an adverse event. Eptinezumab was associated with early and sustained reductions in migraine frequency. Mean MMDs at baseline were approximately 14 days across groups. Mean (standard error) change from baseline in MMDs over the final dosing interval (weeks 61-72) was -6.4 (0.50) with placebo/eptinezumab 100 mg, -7.3 (0.49) with placebo/eptinezumab 300 mg, -7.1 (0.39) with eptinezumab 100 mg, and -7.0 (0.39) with eptinezumab 300 mg. During weeks 61-72, 63-70% of patients demonstrated ≥ 50% reduction in MMDs, and 36-45% demonstrated ≥ 75% reduction. Headache severity and acute medication use reductions, and patient-reported improvements in most bothersome symptom, disease status, quality of life, and work productivity, were observed. Adverse events were generally mild, transient, and similar in frequency/type to previous eptinezumab trials.
 
The long-term effectiveness and safety/tolerability of eptinezumab in patients with migraine and 2-4 prior preventive treatment failures was demonstrated by high completion rates and migraine-preventive benefits sustained for up to 18 months, implying that eptinezumab is a viable long-term treatment option for patients still seeking successful migraine treatments. (Ashina M, Tepper SJ, Gendolla A, et.al., 2023)
 
2025 Update
In September 2024, a direct comparison meta-analysis of randomized controlled studies has evaluated eptinezumab 300 mg against 100 mg. Overall, compared with eptinezumab 100 mg in migraine patients, eptinezumab 200 mg was associated with substantially improved 75% responded rate (OR= 1.34; 95% CI= 1.06 to 1.69; p=0.01), but demonstrated similar monthly migraine days (MD=-0.09, 95% CI=-=-0.09; 95% CI=-0.20 to 0.01; P=0.08), 100% responder rate (OR=1.38; 95% CI=0.94 to 2.02; P=0.10), 50% responder rate (OR=1.20; 95% CI=0.97 to 1.48; P=0.10), migraine 1 day after dosing (OR=0.92; 95% CI=0.72 to 1.18; P=0.52), adverse events (OR=1.13; 95% CI=0.77 to 1.65; P=0.53), nasopharyngitis (OR=1.26; 95% CI=0.74 to 2.14; P=0.40), upper respiratory tract infection (OR=1.25; 95% CI=0.83 to 1.88; P=0.29), sinusitis (OR=1.78; 95% CI=0.95 to 3.33; P=0.07) or nausea (OR=1.26; 95% CI=0.68 to 2.32; P=0.46). Based on results of the trial, researchers have concluded that eptinezumab 300 mg may have better efficacy for migraine patients than eptinezumab 100 mg (Jing, 2024).
CPT/HCPCS:
J3032Injection, eptinezumab jjmr, 1 mg
J3490Unclassified drugs
J3590Unclassified biologics
References: Ashina M, McAllister P, Cady R, Hirman J, Ettrup A.(2022) Efficacy and safety of eptinezumab in patients with migraine and self-reported aura: Post hoc analysis of PROMISE-1 and PROMISE-2. Cephalalgia. 2022 Jul;42(8):696-704. doi: 10.1177/03331024221077646. Epub 2022 Mar 18. PMID: 35302389; PMCID: PMC9218409.

Ashina M, Saper J, Cady R, et al.(2020) Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-I). Cephalalgia 2020 Jan 17; https://journals.sagepub.com/doi/pdf/10.1177/0333102420905132. Accessed April 13, 2020.

Baker B, et al.(2020) Population pharmacokinetic and exposure-response analysis of eptinezumab in the treatment of episodic and chronic migraine. Pharmacol Res Perspect. 2020 Apr;8(2):e00567. doi: 10.1002/prp2.567. PMID: 32155317; PMCID: PMC7064329.

Jing W, Xingchuan L, Zhiguo Y, et.al.(2024) Comparison of eptinezumab 300 mg with 100 mg for the treatment of migraine: a meta-analysis of randomized controlled studies. African Health Sciences. 2024 Oct 6;24(3):393-400.

Lipton RB, Goadsby PJ, Smith J, et al.(2020) Efficacy and safety of eptinezumab in patients with chronic migraine (PROMISE-2). American Academy of Neurology 2020; https://n.neurology.org/content/neurology/94/13/e1365.full.pdf. Accessed April 13, 2020

Silberstein SD, Holland S, Freitag F, et al.(2012) Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults. American Academy of Neurology 2012 Jan 27; https://n.neurology.org/content/78/17/1337.full. Accessed April 15, 2020.

Vyepti [package insert]. Bothell, WA; Lundbeck Seattle BioPharmaceuticals, Inc; February 2020
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