The following is a summary of the “Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial,” published in the March 2023 issue of Neurology by Lipton, et al.
Patients suffering from migraines for whom oral medicines are either ineffective, slow-acting, or intolerable due to nausea and vomiting may find relief with intranasal formulations. Small molecule calcitonin gene-related peptide (CGRP) receptor antagonist zavegepant was evaluated in a phase 2/3 trial before being approved for intranasal administration. This randomized, placebo-controlled, phase 3 trial compared the effectiveness, safety, and time course of zavegepant nasal spray in the acute treatment of migraine with that of a placebo. Adults (aged 18 years) with a history of two to eight monthly attacks of moderate or severe migraine were recruited for this double-blind, randomized, placebo-controlled, multicentre phase 3 trial at 90 academic medical centers, headache clinics, and independent research facilities in the United States. All participants self-treated a moderate to severe migraine attack with either a zavegepant 10 mg nasal spray or a matching placebo (1:1).
Randomization was stratified by the use or non-use of preventative medicine. An independent contract research organization operated and managed an interactive web response system, which was used by study center staff to enroll eligible participants. Group assignments were concealed from the participants, researchers, and benefactors. All randomly assigned participants who took the study medication, had a baseline migraine attack of moderate or severe pain intensity and provided at least one evaluable post-baseline efficacy data point were evaluated for the coprimary endpoints of freedom from pain and freedom from the most bothersome symptom at 2 h after the treatment dose. Safety was examined in all randomly assigned subjects who received at least 1 dose.
A total of 1,978 people were sought out and evaluated for participation between October 27, 2020, and August 20, 2021.
There were 1,405 potential subjects, 703 randomly assigned to receive zavegepant and 702 to receive a placebo, and 1,269 of whom were included in the efficacy analysis set (623 in the zavegepant group and 646 in the placebo group). More people in the zavegepant group reported relief from their pain and other symptoms 2 hours after the treatment dose (147 [24%] of 623 participants vs 96 [15%] of 646 participants, risk difference 88 percentage points, 95% CI 45-131; p0001), and more people in the placebo group reported no relief from their symptoms. Dysgeusia (129 [21%] of 629 in the zavegepant group vs 31 [5%] of 653 in the placebo group), nose pain (23 [4%] vs five [1%]), and nausea (20 [3%] vs seven [1%]) were the most common side effects (2%) in both treatment groups. There was no evidence that zavegepant caused hepatotoxicity.
The nasal spray formulation of zavegepant 10 mg was effective in the short-term management of migraine attacks, and it was well tolerated and safe. Further research is needed to confirm the treatment’s long-term safety and ensure that its efficacy remains consistent among attacks.