Long-term safety and tolerability of zavegepant 10-mg nasal spray with concomitant use of anti-calcitonin gene-related peptide monoclonal antibodies or other select preventive migraine medications: Results from a phase 2/3 open-label study

Abstract

Objective: To evaluate the safety and tolerability of zavegepant (ZAV) when used as needed for acute treatment of migraine in patients taking concomitant preventive migraine medications (anti-calcitonin gene-related peptide monoclonal antibodies [CGRP mAbs] or other select preventive migraine medications [OSPs]).

Background: People with migraine often use preventive and acute treatments concomitantly for breakthrough attacks. ZAV 10-mg nasal spray is the first intranasal, small-molecule CGRP receptor antagonist approved for the acute treatment of migraine with or without aura in adults.

Methods: This was a subgroup analysis of data from a multicenter, single-arm, open-label, phase 2/3 clinical trial that assessed the safety and tolerability of ZAV for the acute treatment of migraine. Participants self-administered 1 ZAV dose/day as needed up to 8 times/month for up to 52 weeks to treat migraine attacks of any severity. Participants were categorized into five cohorts based on their current or concomitant use of preventive treatments: ZAV + CGRP mAbs, ZAV + OSPs, ZAV + CGRP mAbs or OSPs, ZAV monotherapy (ZAVmono), and the overall study population. Adverse events (AEs), clinical laboratory results, and vital signs data were evaluated and summarized descriptively.

Results: A total of 603 participants self-administered ≥1 dose of ZAV and 341 participants (56.6%) completed the study. Among the 603 ZAV-treated participants, 39 (6.5%) received ZAV + CGRP mAbs, 72 (11.9%) received ZAV + OSPs, 103 (17.1%) received ZAV + CGRP mAbs or OSPs (eight participants received both CGRP mAbs and OSPs), and 500 (82.9%) received ZAVmono. Baseline characteristics were similar across cohorts. The mean number of ZAV doses self-administered per month was similar across cohorts (3.1-3.3). The proportion of participants experiencing an AE was similar across cohorts (range: 73.6-76.9%). The most frequent AEs were dysgeusia (range across cohorts: 28.2-41.7%), nasal discomfort (9.7-15.4%), COVID-19 (7.2-8.7%), nausea (4.2-10.3%), back pain (4.4-15.4%), throat irritation (4.4-12.8%), and nasal congestion (5.2-7.7%). Most AEs had mild-to-moderate severity and resolved without treatment. The proportion of participants who discontinued due to an AE was similar across cohorts (range: 4.2-7.7%). No serious AEs related to ZAV treatment occurred. The proportion of participants who experienced a local-irritation AE was similar across cohorts (range: 49.4-51.4%), as was the proportion who experienced a hepatic-related AE (3.8-7.7%). No AEs related to medication-overuse headache, suicidality, or cardiovascular events occurred. No clinically meaningful trends in laboratory test results or vital signs were observed.

Conclusion: Self-administration of ZAV 10-mg nasal spray for the acute treatment of migraine up to 8 times/month for up to 52 weeks appeared well-tolerated irrespective of concomitant use of CGRP mAbs or OSPs.

Keywords: calcitonin gene‐related peptide receptor antagonist; clinical trial; migraine; preventive migraine treatment; safety; zavegepant.