New Migraine Drugs Near Approval

Treatment landscape expected to expand for recurring chronic condition

BRIEFING
October 21, 2021
Medical Director, CVS Caremark
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A migraine is a type of recurring severe headache. Approximately one in every six American adults has experienced a migraine over a three-month period. Headaches are the third most common reason for reproductive-age women to visit emergency rooms.Burch R, Rizzoli P, Loder E. The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends From Government Health Studies. Headache. 2018 Apr;58(4):496-505. doi: 10.1111/head.13281. Epub 2018 Mar 12. PMID: 29527677. According to a 2016 study, the costs associated with health care and lost productivity due to migraines are estimated to be $36 billion each year in the United States alone.https://www.ajmc.com/view/study-summary-costs-associated-with-migraine-in-the-united-states

What is a migraine?

Migraines are considered a neurovascular disorder associated with dysfunction of the cerebral nerve cells and blood vessels. Current scientific findings lead to the belief that the primary dysfunction occurs in the brainstem centers which regulate vascular tone and pain sensation.https://www.fda.gov/drugs/news-events-human-drugs/new-drug-class-employs-novel-mechanism-migraine-treatment-and-prevention

Checkmark Individuals with migraines experience recurring and painful headaches that usually occur only on one side of the head. A migraine can limit a person’s movement. Such headaches must occur five times or more per month to be classified as a migraine.InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Migraine: Overview. [Updated 2018 May 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279373/,Weatherall, Mark W. “The diagnosis and treatment of chronic migraine.” Therapeutic advances in chronic disease vol. 6,3 (2015): 115-23. doi:10.1177/2040622315579627
Checkmark Chronic migraines are defined as having a headache day 15 times or more per month for more than three months duration and having a headache with migraine symptoms at least eight days of each month.https://journals.sagepub.com/doi/pdf/10.1177/0333102417738202
Checkmark During an episode, people can experience sensitivity to light or noise, and vision may be affected. Migraines may last anywhere from four hours to several days.InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Migraine: Overview. [Updated 2018 May 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279373/
Checkmark There is currently no cure for migraine headaches and because of their unpredictability, migraines can impact a person’s ability to work and be productive.Atlas S, Touchette D, Agboola F, Lee T, Chapman R, Pearson S D, Rind D M. Acute Treatments for Migraine: Effectiveness and Value. Institute for Clinical and Economic Review, February 25,2020. http://icer-review.org/material/acute-migraine-evidence-report/

What is a migraine?

Migraines are considered a neurovascular disorder associated with dysfunction of the cerebral nerve cells and blood vessels. Current scientific findings lead to the belief that the primary dysfunction occurs in the brainstem centers which regulate vascular tone and pain sensation.3

Checkmark Individuals with migraines experience recurring and painful headaches that usually occur only on one side of the head. A migraine can limit a person’s movement. Such headaches must occur five times or more per month to be classified as a migraine.4,5
Checkmark Chronic migraines are defined as having a headache day 15 times or more per month for more than three months duration and having a headache with migraine symptoms at least eight days of each month.6
Checkmark During an episode, people can experience sensitivity to light or noise, and vision may be affected. Migraines may last anywhere from four hours to several days.7
Checkmark There is currently no cure for migraine headaches and because of their unpredictability, migraines can impact a person’s ability to work and be productive.8

What is the prevalence of migraines?

  • More than 1 billion people worldwide suffer from migraines, including almost 40 million Americans.https://americanmigrainefoundation.org/,https://www.washingtonpost.com/national/health-science/why-do-women-suffer-more-migraines-than-men/2018/10/12/6ad47e8a-c66b-11e8-b1ed-1d2d65b86d0c_story.html
  • About 18 percent of females suffer from migraines, whereas the rate for males is 6 percent. The prevalence of migraines in children is approximately 10 percent — boys and girls being equally affected.https://migraineresearchfoundation.org/about-migraine/migraine-facts/
  • Women often have their first migraine around the time menses begins.
  • While the occurrence of migraines may diminish over time, some experience migraines with increasing frequency.https://americanmigrainefoundation.org/resource-library/what-is-chronic-migraine/
  • Those with migraines incur more direct medical costs, such as emergency room visits and hospitalizations, than those without migraines.https://doi.org/10.1111/j.1524-4733.2008.00404.x
  • The total annual mean direct medical costs for those with migraines is more than $8,924 higher than those without.https://www.ajmc.com/view/study-summary-costs-associated-with-migraine-in-the-united-states
  • In addition to direct medical costs, indirect costs — absenteeism, disability and decreased productivity — are $2,350 higher than costs for those who do not experience migraines.https://www.ajmc.com/view/study-summary-costs-associated-with-migraine-in-the-united-states

What are the symptoms?

  • Over several days, migraines generally follow a four-phase pattern: early symptoms (or pro-drome), aura, headache and prolonged effects (or post-drome).https://medlineplus.gov/migraine.html
  • Nausea, dizziness, sensory sensitivities and loss of appetite are symptoms that often accompany migraines.Weatherall, Mark W. “The diagnosis and treatment of chronic migraine.” Therapeutic advances in chronic disease vol. 6,3 (2015): 115-23. doi:10.1177/2040622315579627
  • Up to 20 percent of those who have migraines may also experience additional symptoms — visual and sensory aura, fatigue, yawning, neck stiffness — sometimes days before the onset of the debilitating headache.Weatherall, Mark W. “The diagnosis and treatment of chronic migraine.” Therapeutic advances in chronic disease vol. 6,3 (2015): 115-23. doi:10.1177/2040622315579627

What are the causes?

  • Although migraines are believed to primarily be a genetic disorder, stress and certain foods or substances, such as tobacco, can trigger a migraine.https://medlineplus.gov/migraine.html
  • Fluctuations in estrogen have been tied to the occurrence of migraines, especially in perimenopause, which can result in increased hormone imbalances.Pavlović, Jelena M. “Evaluation and management of migraine in midlife women.” Menopause (New York, N.Y.) vol. 25,8 (2018): 927-929. doi:10.1097/GME.0000000000001104

What is the current treatment landscape for migraines?

New Migraine Drugs Near Approval Accordion

Treatments for migraines are classified into acute (taken when a migraine occurs) and preventive (those taken to avoid or minimize a migraine from occurring).
  • Acute medications used to treat a migraine include analgesics, such as ibuprofen, acetaminophen and opiates (limited to refractory cases), triptans and ergot alkaloids.https://americanmigrainefoundation.org/resource-library/migraine-medication/
  • Some preventive medications include onabotulinumtoxinA (Botox) and certain agents within the following classes: antihypertensives, anticonvulsants, antidepressants and calcitonin gene-related peptide (CGRP)-targeted drugs.
  • The U.S. Food and Drug Administration (FDA) approved three drugs in a new class of drugs in 2018 — the CGRP-targeted therapies — specifically designed to help prevent migraines. CGRP has been found to be elevated in blood serum during a migraine.Durham, Paul L. “Calcitonin gene-related peptide (CGRP) and migraine.” Headache vol. 46 Suppl 1,Suppl 1 (2006): S3-8. doi:10.1111/j.1526-4610.2006.00483.x
    • Aimovig (erenumab-aooe), from Amgen, is a self-injected, subcutaneous (SC)-administered drug for the prevention of migraines and was the first of the CGRP class approved by the FDA.https://www.fda.gov/news-events/press-announcements/fda-approves-novel-preventive-treatment-migraine
    • Teva Pharmaceuticals received approval for the self-administered, SC-injected Ajovy (fremanezumab-vfrm) for the preventive treatment of migraines.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761089Orig1s000TOC.cfm
    • Eli Lilly’s Emgality (galcanezumab-gnlm) was approved in 2018 as a preventive treatment for migraines. It is a self-injected, SC drug that also received Breakthrough Therapy designation for treating cluster headaches in 2019.https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-episodic-cluster-headache-reduces-frequency-attacks
CGRP-targeted therapies have continued to evolve to include oral products that have been approved for both acute migraine treatment as well as prevention.
  • AbbVie’s Ubrelvy (ubrogepant), approved in 2019, is an oral CGRP inhibitor for treatment of acute migraines.https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-adults-migraine
  • First approved in 2020 for acute treatment and in 2021 for prevention, Nurtec ODT (rimegepant) from Biohaven Pharmaceuticals is an oral-dosed CGRP inhibitor medication.https://www.fiercepharma.com/pharma/biohaven-migraine-med-becomes-first-dual-acute-preventative-treatment-latest-fda-nod.,https://www.biopharmadive.com/news/biohaven-coric-nurtec-migraine-marketing/603252/
    • Our standard utilization management criteria limit is 16 tablets due to package size of eight per pack.
    • The maximum dose for within 24 hours is 75 mg. For the acute treatment of migraine, 75 mg is recommended to be taken as needed. While 75 mg taken every other day is the recommended dosage for preventive treatment of episodic migraines. The safety of using more than 18 doses in a 30-day period has not been established. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212728s006lbl.pdf
  • Reyvow (lasmiditan), approved in 2019 and launched in 2020, is an oral medication for acute treatment of migraines from Eli Lilly. Reyvow introduced a new class of migraine treatment — the selective serotonin 5-HT1F receptor agonist. https://www.biospace.com/article/eli-lilly-s-reyvow-wins-fda-approval-for-acute-treatment-of-migraine/
  • Vyepti (eptinezumab-jjmr), a CGRP receptor antagonist, received approval in 2020 for the preventive treatment of migraine in adults. Vyepti is an intravenous product from Lundbeck Seattle BioPharmaceuticals. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761119Orig1s000TOC.cfm
  • Impel Biopharma’s Trudhesa (dihydroergotamine) is a treatment for acute migraines administered nasally. Impel received approval in September and launched Trudhesa in October 2021. https://www.globenewswire.com/news-release/2021/09/03/2291459/0/en/Impel-NeuroPharma-Announces-U-S-FDA-Approval-of-TRUDHESA-Dihydroergotamine-Mesylate-Nasal-Spray-for-the-Acute-Treatment-of-Migraine.html
  • Qulipta (atogepant) is an oral CGRP antagonist for the prevention of migraines. AbbVie’s Qulipta received FDA approval in September with its launch in October 2021.https://news.abbvie.com/news/press-releases/fda-approves-qulipta-atogepant-first-and-only-oral-cgrp-receptor-antagonist-specifically-developed-for-preventive-treatment-migraine.htm
    • Qulipta tablets are available in the recommended dosage of 10 mg, 30 mg or 60 mg and taken once daily with or without food.https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215206Orig1s000lbl.pdf
  • Initial formulations in this class have been SC and for migraine prevention and two recently launched orals indicated for treatment, with one now also approved for prevention.

What are the upcoming notable drugs for migraines in the pipeline?

New drugs for migraines currently in the pipeline include:

Checkmark Zavegepant, is a CGRP antagonist in development by Biohaven. It is administered intranasally for acute migraines. Zavegepant may be approved in the fourth quarter of 2022.https://n.neurology.org/content/96/15_Supplement/4976.abstract
Checkmark Qtrypta (zolmitriptan) is delivered using a topical patch. This Zosano Pharma treatment for acute migraines may be approved in the second quarter of 2022.https://www.fiercepharma.com/drug-delivery/zosano-plots-2021-resubmission-for-once-rejected-migraine-patch
Checkmark Rizaport (rizatriptan) is an oral film used to treat acute migraines sublingually in development by InterlGenX and may be approved in the second quarter of 2022.https://www.future-science.com/doi/full/10.4155/tde-2019-0095
Checkmark AXS-07 (meloxicam/rizatriptan) is an oral combination of a nonsteroidal anti-inflammatory drug (NSAID) and a triptan for the treatment of acute migraines that is in development by Axsome Therapeutics. AXS-07 may be approved in the second quarter of 2022.https://www.axsome.com/axs-pipeline/about-axs-07

What cost management strategies are available for migraine therapies?

Checkmark New drugs on the market are expected to increase competition among existing migraine treatments; and a competitive market can help drive down net costs. CVS Health has been able to manage net costs by utilizing the competition in the category. CVS Health uses various strategies to ensure the lowest net cost for migraine drugs for payors and to ensure clinically appropriate medication for patients.
Checkmark Some of the utilization management (UM) techniques available for migraine medication management include:
  • Prior authorization (PA)
  • Quantity limits (QL)
  • Step therapy (ST)
Checkmark For SC formulations, PA and ST are available.
Checkmark For oral formulations, ST is available.
Checkmark Adoption of formularies that exclude drugs in certain categories, such as Standard Control Formulary (SCF) and Advanced Control Formulary (ACF), can help manage costs in these categories. When a product launches, new-to-market review and an assessment of clinical appropriateness inform UM and strategic plan design options, such as tier placement.
Checkmark Our standard UM processes effectively manage utilization and minimize costs associated with uses that are outside the scope of the plan’s pharmacy benefit. Prior to launch, we seek input from external subject matter thought leaders to help understand potential impact. Dedicated resources, including experienced clinicians, closely follow and evaluate the drug pipeline to assist with decisions regarding appropriate formulary placement.
BRIEFING
October 21, 2021
Medical Director, CVS Caremark

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