Efficacy and Safety of Zavegepant Nasal Spray for the Acute Treatment of Migraine: Results of a Phase 3 Double-Blind, Randomized, Placebo Controlled Trial
Kathleen Mullin1, Robert Croop2, Jelena Pavlovic3, Linda Mosher2, Timothy Smith4, Jennifer Madonia2, Meghan Lovegren2, Richard Lipton3
1New England Institute for Neurology and Headache, 2Biohaven Pharmaceuticals, 3Albert Einstein College of Medicine, 4StudyMetrix Research

Compare the efficacy and safety of zavegepant nasal spray with placebo in the acute treatment of migraine.

Zavegepant is the only small molecule CGRP receptor antagonist delivered by nasal spray in late-stage development for the acute treatment of migraine. In a Phase 1 study with healthy subjects, the 10 mg nasal spray was rapidly absorbed (Tmax ~30 minutes). In a dose-ranging study (NCT03872453), zavegepant 10 mg was the optimal dose.

In this phase 3, double-blind, randomized, placebo-controlled trial (NCT04571060), adults with a history of 2-8 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 (MBS) at 2 hours postdose.


Of 1405 randomized subjects, 1269 (mean age 41 years, 83% female) were evaluable for efficacy (zavegepant n=623, placebo n=646). Zavegepant was superior to placebo for pain freedom (23.6% vs 14.9%, p<0.0001) and freedom from the MBS (39.6% vs 31.1%, p=0.0012) at 2 hours postdose. Secondary endpoints included pain relief at 15 minutes (15.9% vs 8.0%, p<0.0001) and 2 hours (58.7% vs 49.7%, p=0.0012); return to normal function at 30 minutes (10.5% vs 6.1%, p=0.0059) and 2 hours (35.8% vs 25.6%, p=0.0001); and sustained pain relief 2 to 48 hours (36.1% vs 29.6%, p=0.013) postdose. The most common (≥2%) adverse events (zavegepant vs placebo) were dysgeusia (20.5% vs 4.7%), nasal discomfort (3.7% vs .8%), and nausea (3.2% vs 1.1%). Most adverse events were mild or moderate; none were serious.


Zavegepant nasal spray was effective for the acute treatment of migraine, achieving its coprimary endpoints and providing onset of pain relief as early as 15 minutes postdose, sustained benefits to 48 hours postdose, and favorable safety and tolerability.