Efficacy of Zavegepant Nasal Spray for the Acute Treatment of Migraine Based on Triptan Treatment Experience: Pooled Results From 2 Randomized, Placebo-Controlled Clinical Trials
Shivang Joshi1, Timothy Smith2, Jelena Pavlovic3, Kathleen Mullin4, Robert Croop5, Jennifer Madonia5, Linda Mosher5, Meghan Lovegren5, Micaela Forshaw5, Richard Lipton3
1Community Neuroscience Servicese, 2StudyMetrix Research, 3Albert Einstein College of Medicine, 4New England Institute for Neurology and Headache, 5Biohaven Pharmaceuticals
Objective:

Compare the efficacy of zavegepant nasal spray with placebo in the acute treatment of migraine based on historical and current triptan experience.

Background:
Zavegepant, an intranasal gepant, is likely to be used in people who do not respond to or cannot take triptans.
Design/Methods:
Post-hoc subgroup analysis based on the pooled results of 2 randomized, double-blind clinical trials comparing the efficacy of zavegepant nasal spray with placebo in the acute treatment of a single migraine attack of moderate to severe pain intensity. Subgroups reporting a history of an insufficient response to ≥1 triptan, current triptan users without a history of insufficient response, and triptan-naïve participants were analyzed. Co-primary efficacy endpoints were 2-hour pain freedom and freedom from the most bothersome symptom (MBS).
Results:

In the pooled population (N=2061; zavegepant n=1014, placebo n=1047), 608 (29.5%) participants had a history of insufficient response to ≥1 triptan (zavegepant=307 [30.3%], placebo=301 [28.7%]), and 1453 (70.5%) had no history of insufficient response to triptans (current use=371 [18.0%], triptan-naïve=1082 [52.5%]). Zavegepant was effective on the coprimary endpoints in current triptan users (pain free: 21.0% vs 11.9%, nominal-p=0.0254, MBS free: 40.0% vs 29.5%, nominal-p=0.0440); participants who were triptan-naïve (nominal-pain free: 24.8% vs 17.4%, nominal-p=0.0029, MBS free: 40.4% vs 34.0%, nominal-p=0.0303); and those with history of insufficient response to ≥1 triptan (pain free: 21.8% vs 12.6%, nominal-p=0.0024; MBS free: 41.0% vs 29.9%, nominal-p=0.0035). Early benefit on pain relief was demonstrated for zavegepant within 15 minutes postdose in triptan-naïve participants (17.6% vs 8.1%, nominal-p<0.0001) and those with an insufficient response to ≥1 triptan (14.3% vs 7.0%, nominal-p=0.0030), the difference in current triptan users was not significant (18.5% vs 14.2%, nominal-p=0.3066).

Conclusions:

Zavegepant nasal spray was effective on both coprimary endpoints for the acute treatment of migraine in adults with and without a history of insufficient response to triptans and current triptan users.

10.1212/WNL.0000000000203946