Zavegepant nasal spray exhibits good efficacy and safety in acute migraine

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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Posted on 26 June, 2023