A Phase 2/3 Open-label, Long-term, Safety Trial of Zavegepant 10 mg Nasal Spray for the Acute Treatment of Migraine (P9-12.002)

Objective:

Evaluate the safety and tolerability of zavegepant 10 mg nasal spray in the acute treatment of migraine.

Background:

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

Design/Methods:

This was a Phase 2/3, 1-year open-label safety study (NCT04408794) of zavegepant for the acute treatment of migraine. Adults aged ≥18 years with a history of 2 to 8 moderate-severe monthly migraine attacks were eligible. Subjects self-administered 1 dose of zavegepant 10 mg nasal spray per day as needed to treat migraine attacks of any severity, up to 8 times per month, for 52 weeks. Months were defined as 4-week intervals. Subjects who took ≥1 dose of zavegepant were included in the analysis.

Results:

Of the 608 subjects entering the long-term treatment phase, 603 were treated with zavegepant 10 mg nasal spray. At baseline, the mean (SD) number of moderate-severe attacks per month was 5.0 (1.89), and 18.1% of treated subjects were using preventive migraine medication. Treatment-emergent adverse events (AEs) reported in ≥5% of subjects were dysgeusia (39.1%); nasal discomfort (10.3%); COVID-19 (7.5%); nausea (6.1%); nasal congestion and throat irritation (5.5% each); and back pain (5.3%). In total, 6.8% of treated subjects discontinued due to AEs; 1.5% discontinued due to dysgeusia. The majority of AEs (96.4%) were mild to moderate in intensity. Of the 7 serious AEs reported, none was considered related to treatment by the investigators. Aminotransferases >3x the upper limit of normal (ULN) occurred in 2.6% of subjects, none of whom had concurrent elevations in bilirubin >2x ULN. Subjects took a mean (SD) of 3.1 (1.6) zavegepant doses per month.

Conclusions:

This 1-year open-label safety study demonstrated favorable safety and tolerability for zavegepant 10 mg nasal spray for the acute treatment of migraine. Disclosure: 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. Ms. Hould has received personal compensation for serving as an employee of Biohaven . Ms. Hould has stock in Biohaven . 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.. 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.