Long-Term Safety of Zavegepant Nasal Spray in Patients with Migraine and Cardiovascular Risk Factors

Long-Term Safety of Zavegepant Nasal Spray in Patients with Migraine and Cardiovascular Risk Factors

Background:

The use of certain migraine treatments (e.g., triptans and ergot derivatives) is contraindicated in patients with cardiovascular disease and requires caution in those with cardiovascular risk factors (RFs).^1,2 Zavegepant, the first small molecule calcitonin gene-related peptide receptor antagonist administered as a nasal spray, is indicated for the acute treatment of migraine with or without aura in adults.³

Purpose/Objectives: The current analysis assessed the long-term safety of zavegepant 10 mg nasal spray in patients with migraine and cardiovascular RFs.

Method:

Data were from a Phase 2/3, 1-year, open-label, safety study of zavegepant for the acute treatment of migraine in adults aged ≥18 years with a history of 2 to 8 moderate or severe migraine attacks per month (NCT04408794). Participants self-administered a single dose of zavegepant 10 mg nasal spray as needed to treat migraine attacks (up to once per day and up to 8 times per month) for up to 52 weeks. In the current analysis, participants receiving at least 1 dose of zavegepant were grouped according to the number of RFs present at baseline (0, 1, or ≥2). Cardiovascular RFs could include uncontrolled hypertension, treatment for hypertension, diabetes, current smoker, treatment with statin, and family history of coronary artery disease.

Results:

On-treatment adverse events (AEs) occurred in 366 (77.7%), 77 (72.6%), and 17 (65.4%) participants in the 0, 1, and ≥2 RF groups. Common AEs were dysgeusia (0 RF=40.3%, 1 RF=37.7%, ≥2 RF=23.1%), nasal discomfort (0 RF=9.3%, 1 RF=14.2%, ≥2 RF=11.5%), and back pain (0 RF=4.2%, 1 RF=10.4%, ≥2 RF=7.7%). Severe AEs occurred in 17 (3.6%), 3 (2.8%), and 2 (7.7%) participants in the 0, 1, and ≥2 RF groups. Serious AEs occurred in 4 (0.8%), 3 (2.8%), and 0 participants in the 0, 1, and ≥2 RF groups. No serious AEs were indicative of cardiovascular ischemic events or considered treatment-related.

Conclusions: Open-label treatment, up to 1 year, with zavegepant 10 mg nasal spray was safe and well tolerated in patients with migraine and cardiovascular RFs. Long-term data in a larger sample of patients with cardiovascular RFs would further characterize the safety profile of zavegepant in this population.

References: 1. Dodick DW, et al. J Prim Care Community Health. 2020;11:2150132720963680.
2. Roberto G, et al. Cephalalgia. 2015;35(2):118-131.
3. Zavzpret (zavegepant) prescribing information. Pfizer Labs; 2023.

Disclosures: This study was sponsored by Biohaven, which was acquired by Pfizer in October 2022. Jelena M Pavlovic Has received research support from the NIH; serves as a consultant/advisory board member, or received honoraria from Allergan/AbbVie, Amgen, Biohaven, and Lundbeck/Alder. Robert Croop serves as a consultant to Pfizer; was employed by Biohaven at the time the clinical study was conducted; was employed by Pfizer at the time the analysis was conducted; and owns stock in Biohaven Ltd. Linda Mosher was an employee of Biohaven at the time the clinical study was conducted; is currently an employee of Pfizer; and owns stock/options in Pfizer and Biohaven Ltd. Jennifer Hould is an employee of, and owns stock/options in, Biohaven. Richard B Lipton: Serves on editorial boards (no renumeration) for Neurology, Cephalalgia; serves as a Senior Advisor (no renumeration) to Headache; Has received research support from the NIH, FDA, National Headache Foundation, and Marx Foundation; has received research grants from Allergan/AbbVie, Amgen, and Novartis; serves as a reviewer for the NIA and NINDS; serves as a consultant/advisory board member or receives honoraria from AEON, Allergan/AbbVie, Amgen, Biodelivery Sciences International Biohaven, CoolTech LLC, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, GlaxoSmithKline, Impel Neuropharma, Lundbeck Manistee, Merck, Novartis, Satsuma, Teva, and Vedanta; receives royalties from Wolff’s Headache (8th ed), Informa; and owns stock/options in Biohaven and Manistee.