Zavegepant for Acute Migraine Treatment 2024
Approximately seventy per cent of persons with migraine have never had a diagnosis by a doctor or been prescribed prescription medication for migraine. This is tragic since migraine occurs in 12% of the population and in 25% of women and 5% of men. It is one of the most common disabling reasons to go to the emergency room.
Nausea occurs in 90% of migraine patients and 70% of them have vomiting and other common migraine symptoms such one-sided, moderate to severe headache, and sensitivity to light and sound.
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This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, Migraine textbook author, Podcaster, YouTube video producer, and Blogger.
Zavegepant has been accepted as a new drug application for internasal treatment of migraine. It is a nasal spray providing headache relief as soon as 15 minutes and lasting 48 hours. Zavegepant is a new “Gepant” type drug, especially useful for migraine patients who have nausea and vomiting with their attacks so that they do not need to take an oral pill. It works faster than the other Gepant drugs.
Zavegepant blocks the calcitonin gene-related peptide (CGRP) which is thought to be the most inflammatory, active chemical released by the migraine process.
How does Zavegepant work?
Migraine is a process in the brain wherein the trigeminal nerve, the ganglia of the trigeminal nerve, and the cerebral arteries release Neurokinan A, Substance P, and CGRP. Zavegepant is a new, specifically acting drug working to block CGRP release.
How CGRP is successful in migraine treatment has been found by the subcutaneous and IV use of preventive drugs like Aimovig and Ajovy for migraine. Zavegepant is a very soluble small molecule CGRP receptor agonist with analgesic and immunomodulating activity. After release Zavegepant targets, binds to, and inhibits the activity of CGRP receptors on mast cells in the brain.
Zavegepant inhibits neurogenic inflammation caused by trigeminal nerve release of CGRP and blocks CGRP receptors in smooth muscle cells within vessels, inhibiting dilation of intracranial arteries. It also suppresses pain transmission by inhibiting the central relay of pain signals from the trigeminal nerve to the caudal trigeminal nucleus.
See where Zavegepant works in the migraine timing cycle.
The Migraine timing Cycle
Zavegepant blocks the movement from 1 to 2, preventing the release of neurochemicals aggravating migraine.
Would Zavegepant have a special place in acute therapy of migraine?
Yes, as a nasal spray, it could be taken by migraine sufferers with nausea and vomiting who do not want to take an oral pill or inject something like sumatriptan subcutaneously.
What are the other currently approved Gepant drugs for migraine acute treatment?
Other drugs are Nurtec ODT (rimegepant), Ubrelvy (Ubrogepant and Qulipta (atogepant), oral drugs in the Gepant class.
What are the other currently available nasal spray treatment drugs?
These drugs are Migranal (dihydroergotamine) and Trudhesa (dihydroergotamine).
Nasal spray administration
What about development of medication overuse headache (MOH) with Zavegepant?
Gepants, like Zavegepant have CGRP blocking action which has not been associated with medication overuse headache, or rebound headache, a major problem with other popular acute migraine drugs, such as the triptans. Triptan develop of medication overuse headache following repeat drug use increases the number of migraine attacks. A gepant use for migraine like Zavegepant would not have this problem.
What do important doctors think about Zavegepant?
Vlad Coric, MD, chief executive officer and chairman of Biohaven, who makes Zavegepant, commented:
"People with migraine want an acute treatment that provides fast, lasting relief from the debilitating symptoms of this disease. If approved, zavegepant would provide a new treatment option for patients who need ultra-rapid relief, in as early as 15 minutes, and for those who experience nausea or vomiting and need a nonoral treatment option.
We have generated robust data from two intranasal zavegepant pivotal trials that were submitted with our NDA and look forward to bringing this new treatment option to people suffering from migraine."
In two pivotal double-blind placebo-controlled studies (NCT04571060, NCT03872453), zavegepant had statistically significant superiority to placebo for freedom from pain and from most bothersome migraine-associated symptom at 2 hours
The most bothersome symptoms were chosen from photophobia, phonophobia, or nausea. Higher rates of pain relief at 15 minutes, return to normal functioning at 30 minutes, and sustained pain freedom at 24 and 48 hours were also significantly higher with zavegepant vs placebo.
Richard B. Lipton, MD, professor and vice chair of Neurology at the Albert Einstein College of Medicine and director of the Montefiore Headache Center, commented:
"Many patients with migraine need treatments other than pills for at least some of their attacks. Swallowing a pill may make nausea worse and if the patient vomits, medication cannot be absorbed. Nasal sprays are a favored option to tablets in many situations.
In addition, many patients dissatisfied with their current acute treatments want faster relief so they can get back to their plans without missing life's important moments. Zavegepant nasal spray will be an important option for patients seeking nonoral therapies and faster relief.
Though head-to-head studies are lacking, relative to triptan nasal sprays, zavegepant should provide favorable safety and tolerability, lack of cardiovascular contraindications and precautions, and a reduced risk of medication overuse."
Elyse Stock, M.D., Chief Medical Officer of Biogen, commented:
"In addition to providing new treatment options for everyday heroes at home, work and school, many of the forty million people in the US with migraine hold high-intensity jobs. When migraine strikes, they need a fast-acting treatment option that enables them to quickly get back to work and keep on working.
The zavegepant profile of ultra-rapid 15-minute onset and durable efficacy through 48 hours with a single dose is uniquely well suited to serve people with migraine."
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All the best.
Britt Talley Daniel MD