Zavegepant Effective in Acute Migraine Regardless of Aura Presence


A statistically significantly higher proportion of patients, both with and without predose aura, achieved 2-hour relief of the most bothersome symptom with zavegepant.

Timothy Smith, MD, chief executive officer and president, Study Metrics Research

Timothy Smith, MD

Post-hoc findings from 2 randomized, double-blind trials assessing zavegepant (Zavzpret; Pfizer), an FDA-approved calcitonin gene-related peptide (CGRP) antagonist, continued to support the therapy’s efficacy as an acute treatment for migraine, regardless of the presence or absence of aura.1

Pooling data from phase 2/3 (NCT03872453) and phase 3 (NCT04571060) studies, 2061 patients who were randomly assigned to either zavegepant or placebo were included. Above all, zavegepant outperformed placebo on the coprimary end point of 2h pain freedom for patients with (23.1% vs 16.6%; P = .0323) and without (23.2% vs 14.3; P <.001) predose aura. As for achieving freedom 2h from most bothersome symptoms (MBS), the CGRP medication continued to be beneficial regardless of aura status (with predose aura: 37.5% vs 29.6%; P = .0292; without predose aura: 41.9% vs 33.4%; P <.0001).

These data were presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, by Timothy Smith, MD, chief executive officer and president, Study Metrics Research. In an interview with NeurologyLive®, Smith provided context on the study, stating, “In previous analyses looking at big databases of response rates using triptans and DHEs (dihydroergotamine), the observation has been made that patients tend to respond a little bit better to those treatments if they do not have aura. We wanted to see if the same kind of observation could be made for zavegepant."

In addition to showing significant results on the co-primary end points, zavegepant demonstrated benefit on pain relief as early as 15 minutes postdose in participants with predose aura (15.3% vs 7.9%; P = .0024) and in participants without predose aura (17.4% vs 9.3%; P <.0001). On pain relief at 2 hours postdose, the therapy continued to be effective over placebo, both for patients with predose aura (60.6% vs 51.6%; P = .0177) and without (58.9% vs 51.0%; P = .0029).

READ MORE: Phase 3 PROGRESS Results Highlight Atogepant’s Benefit in Chronic Migraine

"Typically, prevention medications don’t discriminate between the two [aura vs non-aura]," Smith added. "When it comes down to decision-making in a clinic, patients are just looking for options. As a clinician, you want to try to give them good options and give them something with a good evidence based of information to guide you."

Zavegepant is relatively new to the market, gaining FDA clearance as an acute treatment in March 2023. The third generation, high iffinity, selective, and structurally unique agent had its approval based on the 2 studies used in Smith et al’s analysis presented at AAN 2023. With its approval, zavegepant became the first and only CGRP nasal spray available for patients with migraine, and is anticipated to be available in pharmacies in July 2023.2

"It’s not a vasoconstrictor like triptans, so that gives you more of a level of confort and it also opens you up to treat other patients who might have risk factors thsat would prclude them from using a vasoconstrictor,” Smith said, regarding zavegepant. "This is the only nonoral route for the administration of the CGRP blocker that we have. If patients have nausea, difficulty swallowing a pill, if they need rapid relief, these are reasons we would consider in using a nasal spray version, as opposed to an oral version."

Click here for more coverage of AAN 2023.

1. Smith T, Pavlovic J, Mullin K, et al. Zavegepant nasal spray for the acute treatment of migraine with aura and without aura: pooled results from 2 randomized, placebo-controlled clinical trials. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. 004348.
2. Pfizer’s Zavzpret (zavegepant) migraine nasal spray receives FDA approval. News release. Pfizer. March 10, 2023. Accessed April 28, 2023.
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