Zavegepant Nasal Spray Improves Pain, Function in Patients With Acute Migraine

Compared with placebo, zavegepant provides significantly greater freedom from pain and disability in patients with migraine during a 48-hour period, according to study results published in the Journal of Headache Pain.

In the United States, migraine is the most disabling health condition in patients aged younger than 50 years. Oral triptans are recommended as first-line therapy for migraine. However, some patients experience intolerable side effects or do not receive adequate relief from triptans, and many have contraindications to triptan use. For patients with acute migraine for whom triptans are unsuitable, the American Headache Society and the International Headache Society recommends starting treatment with lasmiditan or a gepant.

Zavegepant is the first calcitonin gene-related peptide (CGRP) receptor antagonist available in a nasal spray. The United States Food and Drug Administration has approved zavegepant for the acute treatment of migraine with or without aura in adults.

Researchers conducted a post hoc analysis of BHV3500-301 (ClinicalTrials.gov Identifier: NCT04571060), a phase 3, double-blind, randomized, placebo-controlled study to assess pain severity and functional disability over a 48-hour period in adult patients with a history of migraine for at least 1 year. Patients with 2 to 8 moderate or severe migraine attacks monthly were randomly assigned to receive zavegepant 10 mg nasal spray (n=703) or placebo (n=702) to treat a single moderately or severely painful migraine attack.

Eligible patients had migraine onset before the age 50 and migraine attacks of 4 to 72 hours’ duration if left untreated. Use of preventive medication for migraine was permitted if the condition was stable for at least 3 months before the study screening visit. Use of CGRP monoclonal antibody therapy was not permitted. Patients with contraindications to triptan use were included if they met the other study criteria.

Pain assessments included pain intensity and functional disability on a 4-point scale and whether patients experienced nausea, photophobia, or phonophobia, rating their most bothersome symptom. The researchers measured pain severity and functional disability at various timepoints before and after zavegepant treatment and calculated the proportion of patients at each pain severity or functional disability state and the time spent in each.

For the analysis, the researchers used missing-not-at-random (MNAR) imputation to fill in missing data at the timepoints. Variables used were patient identification, treatment, timepoint, number of previous triptan failures, baseline pain severity, migraine duration, number of historical monthly moderate or severe migraine attacks, rescue medication use, other pain medications used, and concomitant preventive medications. As a result, the MNAR imputation analysis group included 1269 participants. In the other method, the researchers included only the subset of patients with complete data on pain severity or functional disability at all timepoints; the complete-case analysis group included between 630 and 641 patients. The researchers also used a mixed-effects logistic regression model to assess predictors of functional disability.

Compared with patients in the placebo group, a greater proportion of those in the zavegepant group achieved no or mild pain as early as 15 minutes postdose, despite migraine severity being balanced between groups before the doses were taken. Patients in the zavegepant group spent 2.5 more hours free of migraine pain compared with those in the placebo group.

As early as 30 minutes postdose, a higher proportion of patients in the zavegepant group had normal functioning than those in the placebo group. During the 48-hour study period, patients in the zavegepant group spent an average of 3 more hours with normal functioning than those in the placebo group. Results were similar for both the MNAR analysis group and the complete-case analysis group.

Results of a regression model showed that zavegepant treatment, lower pain severity, fewer baseline monthly migraine days, and absence of photophobia, phonophobia, and nausea were associated with better functioning during the 48-hour study period (P <.05).

Study limitations include missing data, and potentially reduced generalizability as only a single migraine attack was assessed.

The researchers concluded, “These data support the use of zavegepant for providing rapid and sustained freedom from migraine pain and freedom from migraine related disability, particularly for those who would benefit from the nasal CGRP formulation.” 

Disclosure: This research was supported by Pfizer. Please see the original reference for a full list of disclosures.

This article originally appeared on Clinical Pain Advisor