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

Post-hoc subgroup analysis of pooled results from 2 randomized, double-blind clinical trials comparing the efficacy of zavegepant 10 mg nasal spray with placebo in the acute treatment of a single migraine attack of moderate-severe pain intensity (NCT03872453, NCT04571060). Participants with a history of <4 and ≥4 attacks per month over the 3 months before study entry were analyzed. The coprimary endpoints were 2-hour pain freedom and freedom from the most bothersome symptom (MBS).

In the pooled population (N=2061; zavegepant n=1014, placebo n=1047), 523 (25.4%) participants had <4 attacks per month (zavegepant=279 [27.5%], placebo=244 [23.3%]), and 1538 (74.6%) had ≥4 attacks per month (zavegepant=735 [72.5%], placebo=803 [76.7%]). Zavegepant was effective on the coprimary endpoints in participants with <4 attacks per month (pain freedom: 24.0% vs 14.3%, nominal-p=0.0049, MBS freedom: 41.6% vs 32.4%, nominal-p=0.0279) and ≥4 attacks per month (pain freedom: 22.9% vs 15.3%, nominal-p=0.0002, MBS freedom: 40.1% vs 32.0%, nominal-p=0.0009). Benefit on pain relief was demonstrated for zavegepant within 15 minutes postdose in participants with ≥4 attacks per month (16.6% vs 7.7%, nominal-p<0.0001). The difference was nonsignificant for those with <4 attacks per month (17.2% vs 12.3%, nominal-p=0.1008). Benefit on pain relief was demonstrated for zavegepant at 2 hours postdose in participants with ≥4 attacks per month (59.5% vs 50.7%, nominal-p=0.0006). The difference was nonsignificant for those with <4 attacks per month (59.5% vs 52.9%, nominal-p=0.1179).

Zavegepant nasal spray was effective for the acute treatment of migraine in participants with ≥4 and those with <4 attacks per month on the coprimary endpoints of 2-hour pain freedom and MBS freedom.