Compare the efficacy of zavegepant nasal spray with placebo in the acute treatment of migraine in participants with and without aura.

Zavegepant is the only small molecule CGRP receptor antagonist for intranasal administration in late-stage development for the acute treatment of migraine.

This post-hoc subgroup analysis is based on the pooled results of 2 randomized, double-blind clinical trials comparing the efficacy of a 10 mg dose of zavegepant nasal spray with placebo in the acute treatment of a single migraine attack of moderate to severe pain intensity (NCT03872453, NCT04571060). Subgroups reporting the presence or absence of predose aura were analyzed. The co-primary efficacy endpoints were pain freedom and freedom from most bothersome symptom (MBS) at 2 hours (2h) postdose.

In the pooled population (N=2061; zavegepant n=1014, placebo n=1047, mean age 40.8 years, 83.6% female), 688 (33.4%) participants had predose aura (zavegepant=320 [31.6%], placebo=368 [35.1%]), and 1373 (66.6%) had no predose aura (zavegepant=694 [68.4%], placebo=679 [64.9%]). Zavegepant was more effective than placebo on the co-primary endpoints in participants with predose aura (2h pain freedom: 23.1% vs 16.6%, nominal-p=0.0323, 2h MBS freedom: 37.5% vs 29.6%, nominal-p=0.0292) and without predose aura (pain freedom: 23.2% vs 14.3%, nominal-p<0.0001, MBS freedom: 41.9% vs 33.4%, nominal-p=0.0011). Zavegepant demonstrated benefit on pain relief as early as 15 minutes postdose in participants with predose aura (15.3% vs 7.9%, nominal-p=0.0024) and in participants without predose aura (17.4% vs 9.3%, nominal-p<0.0001). Zavegepant demonstrated significant benefit on pain relief at 2 hours postdose in participants with predose aura (60.6% vs 51.6%, nominal-p=0.0177) and in participants without predose aura (58.9% vs 51.0%, nominal-p=0.0029).

Zavegepant 10 mg nasal spray was effective and provided a rapid onset of action for the acute treatment of migraine regardless of the presence or absence of predose aura.