Prevention, Treatment for Migraine Rapidly Evolves, Calling for Development of Novel Drugs


Zavegepant (Zavzpret; Pfizer) is the first and only only CGRP receptor antagonist as a nasal spray for the acute treatment of migraine in adults with and without aura approved by the FDA.

Migraine are recurrent headaches occurring with moderate to severe throbbing and pulsating pain on 1 side of the head, according to the National Institute of Neurological Disorders and Stroke.1 Untreated attacks can last from 4 to 72 hours, usually accompanied with sensitivity to light and/or noise, nausea, and vomiting. Although non-steroidal anti-inflammatory drugs (NASAIDs) are often used to treat migraine, there have been many preventative medications approved to reduce the severity and frequency of migraine, including FDA-approved drugs like enenmab (Aimovig; Amgen), galcanezumab-gnlm (Emgality, Eli Lilly), and rimegepand (Nurtec; Pfizer).1 The treatment landscape for treating and preventing migraine has been rapidly evolving.

Young woman has headache, stress, migraine. | Image Credit: Oleksii -

Oleksii -

Newer treatment options include triptans, which include sumatriptan, zolmitriptan, rizatriptan, which are all selective serotonin agonists; however, these medications are not recommended for individuals who have cardiovascular risks, including ischemic heart disease, stroke, or uncontrolled hypertension.2 Non-steroidal anti-inflammatory drugs like acetaminophen and other combination analgesics are used for as-needed OTC treatment and relief for headaches.

Patients with 4 or more headaches or at least 8 headache days per month should be evaluated for prevention therapy.2 Additionally, they should be considered if the migraine attacks are debilitating despite acute treatment, difficult to tolerate, if there is an overuse of acute headache medications, or if there is a presence of migraine subtype.3

Calcitonin gene-related peptide (CGRP) receptor antagonists have been growing in prevalence in the migraine landscape. CGRPs are produced in the central and peripheral nervous systems, with investigators believing that they can trigger migraine due to effects of neurogenic inflammation.2 As of June 2023, there are 8 CGRPs approved by the FDA in the United States, including 4 monoclonal antibodies and 4 small molecule antagonists. Erenumab, fremanezumab (Ajovy; Teva), galcanezumab, eptinezumab (Veypti; Lundbeck), and atogepant (Qulipta; AbbVie) are for preventative treatment while ubrogepant (Ubrelvy; AbbVie) and zavegepant (Zavzpret; Pfizer) are for acute treatment. Rimegepant (Nurtec; Pfizer) is approved for both prophylaxis and treatment.2

The 4 monoclonal antibodies are subcutaneously injected every month, with the exceptions of fremanezumab (injected every 3 months) and eptinezumab (administered intravenously every 3 months). The small molecule antagonists are typically orally administered, except for zavegepant.2

In March 2023, zavegepant was approved by the FDA as the first and only CGRP receptor antagonist as a nasal spray for the acute treatment of migraine in adults with and without aura.4 The recommended dose is a 10 mg single spray in 1 nostril as needed, with a maximum of 1 spray every 24 hours. There are currently no data on more than 8 doses in a 30-day period.5

The efficacy and safety of zavegepant were evaluated in 2 randomized trials, NCT04571060 and NCT03872453, indicating that zavegepant was statistically superior to the placebo for both coprimary endpoints of freedom of pain and freedom from most bothersome symptom. NCT04571060 also assessed pain relief at 2 hours post dose, return to normal function at 2 hours post dose, and sustained pain freedom from 2 to 48 hours post dose, which were statistically different between zavegepant and the placebo.5

In a study published in The Journal of Headache and Pain, the authors call for further research on alternative therapies for those who do not respond to CGRP receptor agonists, including targeting metabotropic receptors, intracellular targets, and ion channels.6 The study authors added that these pathways could provide insight to underlying mechanisms of migraine and aura as well as the future development of novel medication for the treatment and prevention of migraine.6


  1. National Institute of Neurological Disorders and Stroke. Migraine. National Institute of Health. Updated July 11,2023. Accessed November 13, 2023.
  2. Wilson A. Migraine treatments: past, present, and future. Pharmacy Times. June 21, 2023. Accessed November 13, 2023.
  3. Vinciguerra J. Migraine: much progress made, significantly more needed. Pharmacy Times. May 26, 2023. Accessed November 13, 2023.
  4. Hunter E. FDA approves zavegepant nasal spray for acute treatment of migraine in adults. Pharmacy Times. March 10, 2023. Accessed November 13, 2023.
  5. Holmberg M. Zavzpret from Pfizer. Pharmacy Times. August 16, 2023. Accessed November 13, 2023.
  6. Al-Hassany L, Boucherie DM, Creeney H, et al. Future targets for migraine treatment beyond CGRP. J Headache Pain. 2023;24(1):76. Published 2023 Jun 28. doi:10.1186/s10194-023-01567-4
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