Real-World Data Highlight Patient-Reported Benefits of Intranasal Zavegepant for Acute Migraine

In a real-world study conducted at the Cleveland Clinic, patients using 10-mg intranasal zavegepant (Zavzpret; Pfizer) for acute migraine reported meaningful pain relief, improved daily functioning, and high willingness to reuse the therapy through the validated migraine treatment optimization questionnaire-5 (MTOQ-5).1

Presented at the 2025 American Headache Society (AHS) Annual Meeting, lead author Eric Dunn, DO, a neurologist at Cleveland Clinic, and colleagues evaluated patient-reported outcomes of individuals using 10-mg intranasal zavegepant for acute migraine treatment. Overall, the drug exemplified encouraging results, including benefits on pain relief, functional improvement, and a high willingness to reuse. The data, which involved patient responses to the MTOQ-5, a validated instrument for measuring migraine treatment optimization, offer an early glance at the effectiveness and tolerability of this third-generation calcitonin gene-related peptide (CGRP) receptor antagonist in clinical practice.

The study population was 90% female with a mean age of 46.6 years (range 20-83) and a mean BMI of 29.1 kg/m2. Each patient received 9 doses, on average. As for acute efficacy, 45.0% of patients reported achieving complete pain relief within 2 hours of treatment at least half the time, 28.3% reported this benefit less than half the time, and 26.7% never achieved pain relief within that timeframe.

Zavegepant, approved in 2023, is a third-generation, non-oral, intranasal CGRP antagonist designed to offer a rapid-acting alternative to oral medications for acute migraine. Although a phase 3 clinical trial already demonstrated its safety and efficacy, questions remained regarding its consistency and tolerability in real-world use. Thus, the retrospective study, presented at the 2025 American Headache Society (AHS) Annual Meeting, aimed to fill that gap by assessing patient outcomes using validated and supplemental survey tools.

“While clinical trials have shown zavegepant to be effective for acute migraine treatment, understanding how it performs in real-world settings is critical to guiding treatment decisions,” Dunn et al wrote.1 “Our findings suggest that patients are experiencing meaningful relief and functional improvement with this therapy outside of controlled trial environments.”

The analysis comprised patients who received at least two doses of 10-mg intranasal zavegepant. Of the 99 patients surveyed, 60 met eligibility and completed the MTOQ-5 and additional questions assessing pain relief, most bothersome symptom (MBS) resolution, and use of rescue medications, adverse effects, and overall satisfaction. Age, gender, race, and BMI were also included to further strengthen the data.

A subset of patients experienced even more rapid relief: 28.3% reported being pain free within 31-60 minutes, and 16.7% in 30 minutes or less. Sustained relief, defined as pain freedom for at least 24 hours after 1 dose, was reported half the time or more by 43.3% of patients, less than half the time by 23.3%, and never by 33.3%.1

READ MORE: Survey Data Highlights Real-World Use of Rimegepant for Short-Term Migraine Prevention

Further findings around functionality indicated that zavegepant may help reduce the unpredictability of migraine attacks. Overall, 60.0% of patients reported returning to normal activities at least half the time after using the treatment, and 71.7% felt comfortable planning daily activities around the medication at least half the time.1

CGRP contributes to pain and inflammation by widening blood vessels and transmitting pain signals. CGRP receptor antagonists, like zavegepant, work by blocking these receptors to interrupt that process and relieve symptoms. With its 2023 approval, zavegepant became the first CGRP antagonist available as a nasal spray, allowing for fast absorption and quick relief. The drug acts consistently across patients on a biological level, but factors like attack severity, timing of use, and individual variation influence how often patients experience noticeable relief.2

Migraine affects nearly 2.81 billion people worldwide, with a steadily rising global burden and it has significant impact on daily functioning and quality of life, particularly among females of reproductive age. Despite the availability of preventive and acute therapies, many patients continue to suffer breakthrough attacks, variable treatment response, and persistent interictal disruptions that interfere with work, relationships, and emotional well-being.3

These real-world findings support the potential use of zavegepant as part of a broader “toolbox” approach to migraine care, especially for patients seeking fast-acting, non-oral treatments like this one. The authors note that while these early results are promising, further studies with larger patient populations and extended follow-up are needed to better understand the long-term role of the drug in clinical practice. As the first retrospective study using MTOQ-5 to assess real-world outcomes of intranasal zavegepant, this work meaningfully contributes to the growing body of evidence on CGRP-targeted therapies.

“Further real-world follow-up with larger sample sizes are needed to validate these findings,” the investigators noted. “Long-term implications of real-world outcomes will help better define the role of zavegepant within the toolbox approach of therapeutics.”1

REFERENCES:
1.Dunn E, Mays M, Ong B, et al. Real-world outcomes of zavegepant use in a tertiary care setting using Migraine Treatment Optimization Questionnaire-5 (MTOQ-5). Presented at: Frontier (P-261), American Headache Society Annual Scientific Meeting; 2025; Cleveland Clinic, Cleveland, OH.
2.Flavin B. Mind over migraine: Disease burden, innovative therapies, and managed care trends in treating migraine disease. Journal of Managed Care & Specialty Pharmacy. 2025;31(7-a Suppl):S1-S13. doi:https://doi.org/10.18553/jmcp.2025.31.7-a.s1
3.Wattiez AS, Sowers LP, Russo AF. Calcitonin gene-related peptide (CGRP): role in migraine pathophysiology and therapeutic targeting. Expert Opinion on Therapeutic Targets. 2020;24(2):91-100. doi:https://doi.org/10.1080/14728222.2020.1724285

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