Zavegepant Meets Co-Primary Endpoints for Treatment of Acute Migraines in Adults

The phase 3 pivotal clinical trial of zavegepant met its co-primary endpoints, demonstrating that a 10-mg dose of the nasal spray was more effective than the placebo in both in terms of freedom from pain and the most bothersome symptom at 2 hours after the dose.

Zavegepant is an investigational calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine.

“The results from this study demonstrate zavegepant’s potential as an effective acute nasal spray treatment for migraine,” Richard Lipton, MD, from the Department of Neurology at the Albert Einstein College of Medicine, said in a statement. “This was the first phase 3 clinical trial of a non-oral CGRP receptor antagonist developed for the acute treatment of migraine in adults. With this evidence of sustained treatment benefits, good tolerability and an alternative administration method, I believe zavegepant has the potential to fill an important gap in the available options for the acute treatment of migraine.”

Additionally, zavegepant demonstrated relief from migraine pain within 15 minutes, lasting up to 48 hours for many individuals.

In the trial, 1405 individuals were randomized to receive a single 10 mg-dose of either zavegepant or a placebo. Participants experienced 2 to 8 moderate or severe migraine attacks per month, and their untreated attacks lasted a mean of 30.8 hours.

During the study, the individuals identified their most bothersome symptom associated with migraines, including nausea, phonophobia, and photophobia; recorded their headache pain intensity based on a 4-point scale; and recorded their level of functional disability immediately before dosing the treated attack and at various intervals post-dose.

Investigators found that zavegepant was effective in treating acute migraine, measured by superiority to the placebo on the co-primary efficacy endpoints. Further, zavegepant was more effective than the placebo in 13 of 17 secondary endpoints, which included treatment benefits for pain relief beginning as early as 15 minutes and sustained pain relief from 2 through 48 hours after the dose.

For the 14th endpoint, which was return to normal function at 15 minutes post-dose, there was not a significant difference between both arms of the study. The remaining secondary endpoints were not formally tested.

Treatment with zavegepant was also associated with higher rates of return to normal function ability at 30 minutes and 2 hours post-treatment.

“The intranasal formulation for zavegepant embodies breakthrough innovation in patient-centric drug development,” James Rusnak, MD, PhD, senior vice president, chief development officer of internal medicine and hospital and global product development at Pfizer, said in the statement. “If approved by the FDA, zavegepant has the potential to be a significant new treatment option for people with migraine, particularly those who desire fast-acting relief or would benefit from an alternative delivery method.”

Zavegepant was generally well tolerated in the study, with the most common adverse events (AEs) in either treatment group dysgeusia, occurring in 20.5% of zavegepant individuals compared with 4.7% of those taking the placebo; nasal discomfort, occurring in 3.7% and 0.8%, respectively; and nausea, occurring in 3.2% and 1.1%, respectively.

The safety profile was consistent with earlier studies, and no serious AEs were reported in treated individuals. The study results were published in The Lancet Neurology.

Reference

Pfizer announces The Lancet Neurology has published phase3 data for zavegepant for the acute treatment of migraine in adults. Pfizer. News release. February 16, 2023. February 24, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-lancet-neurology-has-published-phase-3