Pfizer announces publication of Phase 3 data for zavegepant in migraine

Pfizer announced publication of results in The Lancet Neurology from the Phase 3 pivotal clinical trial of zavegepant, an investigational calcitonin gene-related peptide receptor antagonist nasal spray for the acute treatment of migraine. The study met its co-primary endpoints, showing that a single 10 mg dose of zavegepant was more effective than placebo for both pain freedom and freedom from the most bothersome symptom at two hours post-dose. Additionally, zavegepant demonstrated relief from migraine pain in 15 minutes, with relief lasting up to 48 hours for many patients. Zavegepant was well tolerated, and there were no serious adverse events reported in treated participants. In the trial, 1,405 people were randomized to receive a single 10 mg dose of either zavegepant or placebo. Participants historically experienced two to eight moderate or severe migraine attacks per month, and their untreated attacks lasted a mean of 30.8 hours. During the study, participants recorded their migraine headache pain intensity based on a four-point scale, identified their current MBS associated with migraine and recorded their level of functional disability immediately before dosing the treated attack and at various intervals post-dose. Zavegepant was demonstrated to be effective in the acute treatment of migraine, as measured by superiority to placebo on the co-primary efficacy endpoints of pain freedom and freedom from the MBS at two hours post-dose. Additionally, zavegepant was more effective than placebo on 13 of the 17 secondary endpoints, including treatment benefits for pain relief beginning as early as 15 minutes and sustained pain relief from two through 48 hours post-dose. On the 14th endpoint, return to normal function at 15 minutes post-dose, the difference between zavegepant and placebo was not significant. Consequently, in keeping with the analysis plan, the remaining secondary endpoints were not formally tested. Treatment with zavegepant was also associated with higher rates of return to normal functional ability at 30 minutes post treatment and two hours. Zavegepant was well tolerated in this study. The most common adverse events in either treatment group were dysgeusia, occurring in 20.5% of zavegepant patients as compared to 4.7% of patients on placebo, nasal discomfort, occurring in 3.7% of zavegepant patients as compared to 0.8% of patients on placebo, and nausea, occurring in 3.2% of zavegepant patients and 1.1% of patients on placebo. The AE safety profile was consistent with earlier studies of zavegepant. There were no serious AEs reported in treated participants, and no signal of hepatotoxicity due to zavegepant was identified in the trial.