A phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of zavegepant for the acute treatment of migraine in Asian adults

In East Asia, migraine may be underdiagnosed and undertreated, resulting in a substantial unmet need for better treatment options. The aim of the study was to evaluate the efficacy and safety of zavegepant 10 mg nasal spray for the acute treatment of migraine in Asian adults. This Phase 3, randomized, double-blind, placebo-controlled study was conducted in 59 clinical sites in 3 regions in Asia (Chinese Mainland, South Korea, and Taiwan). Participants were adults with ≥ 1-year history of migraine. Participants were randomly assigned (1:1) to receive zavegepant 10 mg nasal spray or placebo to treat a single migraine attack of moderate or severe pain intensity. Co-primary efficacy endpoints were the percentage of participants with freedom from pain (pain intensity of none) at 2 h post-dose and percentage of participants with freedom from (absence of) the most bothersome symptom (MBS) at 2 h post-dose that was present before dosing (selected from nausea, photophobia, or phonophobia). Safety assessments were based on adverse events (AEs) and laboratory tests. The study was conducted between November 29, 2023, and May 30, 2025. A total of 1346 participants were evaluable for efficacy (zavegepant n = 677, placebo n = 669). The study met its objective on the co-primary endpoints at 2 h post-dose: 23.2% (zavegepant) vs. 14.1% (placebo) ( p < 0.0001) of participants had pain freedom (treatment difference 9.2%, corresponding to a number needed to treat of approximately 11), and 52.7% (zavegepant) vs. 39.9% (placebo) ( p < 0.0001) of participants had MBS freedom (treatment difference 12.8%, corresponding to a number needed to treat of approximately 8). Statistical significance was also achieved on 6 of the 8 key secondary endpoints, including early-onset pain relief at 15 min post-dose and sustained pain relief from 2 to 48 h post-dose. The overall incidence of AEs was generally comparable to placebo. The majority were mild in severity, considered not related to the study intervention and resolved without treatment. Zavegepant demonstrated a hepatic safety profile comparable to placebo. Zavegepant 10 mg nasal spray demonstrated efficacy superior to placebo, and was well tolerated in Asian adults with migraine, with a favorable safety profile. Clincialtrials.gov NCT05989048. https://clinicaltrials.gov/study/NCT05989048 First registered August 3, 2023.