Efficacy and Safety of Zavegepant Nasal Spray for the Acute Treatment of Migraine: Results of a Phase 3 Double-Blind, Randomized, Placebo Controlled Trial

Abstract text (incl. figure legends and references)

Objective

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

Methods

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 co-primary endpoints were 2-hour freedom from pain and the most bothersome symptom (MBS).

Results

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 2-hour freedom from pain (23.6% vs 14.9%, P<.0001) and 2-hour MBS freedom (39.6% vs 31.1%, P=.0012). Secondary endpoints included pain relief at 15 minutes (15.9% vs 8.0%, P<.0001) and 2 hours (58.7% vs 49.7%, P=.0012); return to normal function at 30 minutes (10.5% vs 6.1%, P=.0059) and 2 hours (35.8% vs 25.6%, P=.0001); and sustained pain relief 2 to 48 hours (36.1% vs 29.6%, P=.013) postdose. Figure 1 summarizes outcomes for the coprimary and secondary endpoints; Figure 2 presents pain relief from 15 minutes through 2 hours 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.

Conclusions

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