Home > Neurology > AAN 2023 > Headache and Migraine > Zavegepant nasal spray exhibits good efficacy and safety in acute migraine

Zavegepant nasal spray exhibits good efficacy and safety in acute migraine

Presented by
Prof. Richard Lipton, Albert Einstein College of Medicine, NY, USA
Conference
AAN 2023
Trial
Phase 3
Doi
https://doi.org/10.55788/3f0abdc4

In a phase 3 trial, zavegepant 10 mg nasal spray was effective for the acute treatment of migraine, demonstrating onset of efficacy as early as 15 minutes post-dose, with sustained benefit. Zavegepant had a favourable safety and tolerability profile: most adverse events were mild or moderate and none were serious.

Non-oral acute therapies for migraine are recommended when oral forms are associated with inadequate response, slow onset of action, or poor tolerability. Rapid onset effect is a priority for many patients with migraine, said Prof. Richard Lipton (Albert Einstein College of Medicine, NY, USA), who presented the study results [1]. He added that most migraine patients prefer nasal sprays to injectables. Zavegepant is the only small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist delivered by nasal spray in late-stage development for the acute treatment of migraine. Its effects and safety were compared with a placebo in a phase 3, double-blind, randomised trial (NCT04571060).

The participants were adults with typically 2–8 moderate or severe monthly migraine attacks. They self-administered 1 dose of 10 mg zavegepant nasal spray or a matching placebo to treat 1 migraine attack. The coprimary efficacy endpoints were freedom from pain and freedom from the most bothersome symptom 2 hours after the intervention.

Participants had a mean age of 41 years; 83% were women. The most bothersome symptom was photophobia in 60.4%, nausea in 24.7%, and phonophobia in 15.0%. A total of 1,269 participants were evaluable for efficacy. Prof. Lipton said that zavegepant nasal spray relieved pain as early as 15 minutes post-dose (15.9% vs 8.0%; P<0.0001). Within 2 hours of administration, significantly more patients achieved freedom from pain (23.6% vs 14.9%; P<0.0001). Zavegepant was superior to the placebo in 13 prespecified secondary endpoints (see Table). Among these endpoints, Prof. Lipton highlighted a return to normal function after 2 hours (“a highly significant difference”) and sustained pain relief 15 minutes post-dose, both of which are highly valued by patients.

Table: Secondary efficacy endpoints in a pre-specified hierarchical order [1]



Most adverse events were mild or moderate; none were serious. The most common adverse events were dysgeusia (20.5% vs 4.7%), nasal discomfort (3.7% vs 0.8%), and nausea (3.2% vs 1.1%). There was no signal of hepatoxicity.

Additional trials are needed to establish the long-term safety and consistency of effect across attacks. In conclusion, Prof. Lipton said: “It is exciting to now have a non-oral option for migraine patients who benefit from the class of CGRP receptor antagonists.”

  1. Mullin K. Efficacy and safety of zavegepant nasal spray for the acute treatment of migraine: Results of a Phase 3 double-blind, randomized, placebo controlled trial. PL5.002, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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