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 (P9-12.003)

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. Disclosure: Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Joshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lilly. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Currax. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Relivion. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nerivio. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axiome. Dr. Joshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven. Dr. Joshi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Joshi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbvie. Dr. Joshi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amgen. Dr. Joshi has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Lilly. Dr. Joshi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Joshi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Impel. Dr. Joshi has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biohaven. The institution of Dr. Joshi has received research support from Lilly . The institution of Dr. Joshi has received research support from Biohaven. The institution of Dr. Joshi has received research support from Amgen. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Nocira. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vorso/Nesos. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alder/Lundbeck. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. The institution of Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. The institution of Dr. Smith has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurolief. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nocira. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theranica. The institution of Dr. Smith has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. The institution of Dr. Smith has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbvie/Allergan. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biohaven. The institution of Dr. Smith has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Lilly. Dr. Smith has stock in United Health Group. The institution of Dr. Smith has received research support from Aeon. The institution of Dr. Smith has received research support from Alder/Lundbeck. The institution of Dr. Smith has received research support from Alnylam. The institution of Dr. Smith has received research support from Amgen. The institution of Dr. Smith has received research support from Abbvie/Allergan. The institution of Dr. Smith has received research support from Biohaven. The institution of an immediate family member of Dr. Smith has received research support from Eliem Pharmaceuticals. The institution of Dr. Smith has received research support from Lilly. The institution of Dr. Smith has received research support from Pfizer. The institution of Dr. Smith has received research support from Nocira. The institution of Dr. Smith has received research support from Novo Nordisk. The institution of Dr. Smith has received research support from Teva. The institution of Dr. Smith has received research support from Theranica. The institution of Dr. Smith has received research support from Vorso/Nesos. Dr. Smith has a non-compensated relationship as a Board Member with National Headache Foundation that is relevant to AAN interests or activities. Dr. Pavlovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Vorso. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Mullin has received personal compensation in the range of $0-$499 for serving as a Consultant for Theranica. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biohaven. Dr. Mullin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Croop has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Dr. Croop has stock in Biohaven Pharmaceutical Holding Co Ltd. Dr. Croop has received intellectual property interests from a discovery or technology relating to health care. Jennifer Madonia has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Jennifer Madonia has stock in Biohaven Pharmaceuticals. Mrs. Mosher has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Mrs. Mosher has stock in Biohaven Pharmaceuticals. Meghan Lovegren has received personal compensation for serving as an employee of Biohaven Pharmaceutials, Inc.. Meghan Lovegren has stock in Biohaven Pharmaceuticals, Inc.. Micaela Forshaw has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Micaela Forshaw has received stock or an ownership interest from Biohaven Pharmaceuticals. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care.