The US Food and Drug Administration (FDA) today approved zavegepant, a calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray, for the acute treatment of migraine with or without aura in adults. The novel anti-CGRP formulation for intranasal delivery is the first and only one of its kind, according to an announcement by manufacturer Pfizer.
To be marketed as Zavzpret, the company anticipates the product will be available in July 2023.
Zavegepant is a third generation, high affinity, selective and structurally unique small molecule CGRP antagonist and the only such molecule in clinical development with both intranasal and oral formulations.
"The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medication,” Angela Hwang, chief commercial officer, president, Global Biopharmaceuticals Business, Pfizer, said in the statement.
The FDA based its decision on 2 pivotal randomized, placebo-controlled clinical trials in which zavegepant proved statistically superior to placebo on the required coprimary end points of freedom from pain and from an individual’s most bothersome symptom (MBS) at 2 hours post-dose.
The pivotal phase 3 study, the first of a non-oral CGRP receptor antagonist developed for acute migraine treatment in adults, was published in The Lancet Neurology. The study was conducted at 90 US locations and comprised a final cohort of 1405 participants aged ≥18 years with a history of 2 to 8 moderate or severe migraine attacks per month with untreated attacks that lasted a mean of 30.8 hours.
Randomization was to a receive a single dose of either zavegepant 10 mg nasal spray (n=703) or placebo (n=702). Randomization was stratified by use or nonuse of preventive medication.
At 2 hours after the treatment dose, more participants in the zavegepant group than in the placebo group had freedom from pain (24% vs 15%, P<.001) and freedom from MBS (40% vs 31%, P=.001). Zavegepant also was more effective than placebo on 13 of the 17 prespecified secondary endpoints, including treatment benefits for pain relief beginning as early as 15 minutes and sustained pain relief from 2 through 48 hours post-dose.
Treatment with zavegepant was also associated with higher rates of return to normal functional ability at 30 minutes and at 2 hours post-treatment.
"When a migraine hits, it has a significant negative impact on a person’s daily life,” Kathleen Mullin, MD, associate medical director, New England Institute for Neurology & Headache, Stamford, CT, said in the statement.
"Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, ZAVZPRET offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly."
Zavegepant was well tolerated during the clinical trials with a safety profile consistent with earlier studies of the drug. The most common adverse events reported in at least 2% of zavegepant-treated patients and more frequently than among placebo-treated participants were e dysgeusia (21% vs 5%) nasal discomfort (4% vs 1%), and nausea (3% vs 1%).