Zavegepant nasal spray safe and effective treatment for acute migraine
Presenter: Richard B. Lipton, MD, Albert Einstein College of Medicine, Bronx, NY
Efficacy and safety of zavegepant nasal spray for the acute treatment of migraine: Results of a phase 3 double-blind, randomized, placebo controlled trial. Presented April 25, 2023.
Intranasal formulations can provide treatment options for migraine patients who do not respond to oral drugs, which may be slow-acting, or are intolerable because of nausea and vomiting. Zavegepant is the only small molecule calcitonin gene-related peptide (CGRP) receptor antagonists delivered by nasal spray that is in late-stage development for the acute treatment of migraine.
In a phase II/III double-blind, randomized, placebo-controlled, dose-ranging trial, single doses of 10 or 20 mg zavegepant were effective for the acute treatment of migraine, with a favorable safety profile, according to presenter Richard B. Lipton, MD, of Albert Einstein College of Medicine, Bronx, NY. “The exciting thing about zavegepant is we now have a non-oral option for patients with migraine who benefit from acute treatment or have prominent nausea or rapid onset of pain and are looking for rapid relief, or who are unsatisfied with the treatments they are now using,” Lipton said. “Migraines are certainly not a one-size fits all condition.”
In this session, Lipton presented results from a phase III, double-blind, randomized, placebo- controlled trial in which adults with a history of 2 to 8 moderate or severe monthly migraine attacks self-administered 1 dose of zavegepant 10 mg nasal spray or placebo to treat 1 migraine attack of moderate or severe pain intensity. The coprimary efficacy endpoints were freedom from pain and freedom from the most bothersome symptom at 2 hours post-dose.
A total of 1,269 patients (mean age 41 years, 83% female) were randomized to zavegepant (623 patients) or placebo (646 patients). At 2 hours after the treatment dose, significantly more participants in the zavegepant group had pain freedom (23.6%) than in the placebo group (14.9%). Zavegepant also led to significantly more freedom from the most bothersome symptoms (39.6% vs 31.1%).
Among secondary endpoints, zavegepant was also significantly superior to placebo in pain relief at 15 minutes (15.9% vs 8.0%) and 2 hours (58.7% vs 49.7%); return to normal function at 30 minutes (10.5% vs 6.1%) and 2 hours (35.8% vs 25.6%); and sustained pain relief 2 to 48 hours (36.1% vs 29.6%) post-dose.
In addition, the drug exhibited a favorable safety and tolerability profile. The most common adverse events at least 2% greater for zavegepant than placebo were dysgeusia (20.5% vs 4.7%), nasal discomfort (3.7% vs 0.8%), and nausea (3.2% vs 1.1%). Most adverse events were mild or moderate, and there were no serious adverse events after dosing, Lipton said. There was no sign of hepatotoxicity. Long-term safety studies have been completed, although data are not yet available.
In conclusion, Lipton said, “Zavegepant 10 mg nasal spray demonstrated rapid onset of efficacy and sustained benefit. The trial met coprimary endpoints and provided pain relief as early as 15 minutes post-dose. Rapid return to normal function occurred as early as 30 minutes post-dose and pain relief and pain freedom were sustained throughout 48 hours with one dose.”
References
Croop R, Madonia J, Stock DA, et al. Zavegepant nasal spray for the acute treatment of migraine: A phase 2/3 double-blind, randomized, placebo-controlled, dose-ranging trial. Headache 2022; 62(9):1153-1163. doi:10.1111/head.14389. Pub 2022 Oct 14.
Lipton RB, Croop R, Stock DA, et al. Safety, tolerability, and efficacy of zavegepant 10 mg nasal spray for the acute treatment of migraine in the USA: a phase 3, double-blind, randomised, placebo-controlled multicentre trial. Lancet Neurol 2023; 22(3):209-217. doi:10.1016/S1474-4422(22)00517-8. Erratum in: Lancet Neurol 2023; 22(5):e7. PMID: 36804093.
Mullin K, Croop R, Pavlovic J. Efficacy and safety of zavegepant nasal spray for the acute treatment of migraine: Results of a phase 3 double-blind, randomized, placebo controlled trial. Presented at the 75th Annual Meeting of the American Academy of Neurology, April 25, 2023. https://index.mirasmart.com/aan2023/PDFfiles/AAN2023-001660.html
Disclosures
Richard B. Lipton, MD
Dr. Lipton has received compensation for serving as a consultant for Allergan/Abbvie, Amgen, Biohaven, Eli Lilly, Lundbeck, GlaxoSmithKline, Teva Pharmaceuticals, Vedanta Biosciences, Merck, Satsuma Pharmaceuticals, Eli Lilly, and Grifols; he has received compensation for serving on a scientific advisory or data safety monitoring board for Allergan/Abbvie, Biohaven, Eli Lilly, and Lundbeck; and he has stock in Biohaven and Manistee pharmacies. The institution of Dr. Lipton has received research support from Amgen, Allergan/Abbvie, Axsome, Charleston Labs, Eli Lilly, Gammacore, Satsuma, and Teva Pharmaceuticals, as well as from the National Institutes on Health, National Institute on Neurological Disorders and Stroke, National Institute on Aging, and Veterans Administration.