Zavegepant (Zavzpret) is the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray approved by the FDA for acute migraine treatment in adults.
On March 10, 2023, Pfizer’s zavegepant (Zavzpret)—the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for acute migraine treatment in adults—was approved by the FDA.1 For the nearly 40 million Americans living with migraines, this approval provides an alternative option for relief, especially for those who have contraindications or poor responses to triptans and other acute migraine medications.
“When a migraine hits, it has a significant negative impact on a person’s daily life,” said Kathleen Mullin, MD, associate medical director at the New England Institute for Neurology and Headache, in a press release.1 “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works.”
Drug Topics spoke with Pfizer to learn more about zavegepant and its approval.
With the FDA approval of zavegepant in March, patients with migraine were given another option to oral medications. What makes zavegepant unique compared to other therapies?
Zavzpret is innovative, as it is the first and only calcitonin gene-related peptide (CGRP) receptor antagonist available as a nasal spray. It is indicated for the acute treatment of migraine with or without aura in adults. It is not indicated for the preventive treatment of migraine.
There are no head-to-head studies comparing Zavzpret to other acute migraine treatments. Zavegepant is fast-acting; in clinical studies, zavegepant demonstrated the ability to provide pain freedom and freedom from most bothersome symptom at two hours post-dose, as well as pain relief at 2 hours post-dose, with some patients experiencing pain relief as early as 15 minutes post-dose. Zavegepant provides a new treatment option for people with migraine who desire quick relief from their migraine symptoms or when oral medications are not an option.
Zavegepant is the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine with or without aura in adults. Can you explain the importance of CGRP receptor antagonists in migraine treatment?
Small molecule CGRP receptor antagonists represent the newest class of drugs for the treatment of migraine. Blocking the CGRP receptor has been shown to reduce pain and symptoms during a migraine attack by inhibiting pain signaling, inhibiting vasodilation without vasoconstrictive effects, and inhibiting neurogenic inflammation. In addition, CGRP signal-blocking therapies have not been associated with medication overuse headache or rebound headache.
The FDA approval of zavegepant was based on the results from 2 clinical studies. Can you discuss what these studies found on the efficacy, tolerability and safety profiles of zavegepant?
In both trials, zavegepant was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from the most bothersome symptom at two hours post-dose.
In its pivotal Phase 3 study which was published in The Lancet Neurology,2 zavegepant was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours post-dose. Study results also demonstrated pain relief at 2 hours post-dose, with some patients experiencing pain relief as early as 15 minutes post-dose, in a prespecified secondary endpoint vs placebo.
Zavegepant was generally well tolerated in clinical trials. The most common adverse reactions reported in at least 2% of patients treated with zavegepant…were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting.
Were there any important or significant adverse reactions in either of the studies?
Hypersensitivity reactions, including facial swelling and urticaria, have occurred with zavegepant. If a hypersensitivity reaction occurs, patients should discontinue zavegepant and initiate appropriate therapy.
Now that zavegepant is available in pharmacies in the United States, what important information about the medication should pharmacists know for their patients?
Zavegepant is supplied in a box of 6 unit-dose devices. One spray in 1 nostril is 1 treatment to be taken as needed, up to once per day. The safety of treating more than 8 migraine attacks in a 30-day period has not been established.