Abstract text (incl. figure legends and references)

Objective

Evaluate the safety of zavegepant 10 mg nasal spray, the only small molecule CGRP receptor antagonist (gepant) for intranasal administration in late-stage development for the acute treatment of migraine.

Methods

This was a Phase 2/3, 1-year open-label safety study (NCT04408794) of zavegepant nasal spray for the acute treatment of migraine. Adults aged ≥18 years with a history of 2 to 8 moderate-severe monthly migraine attacks were eligible. Use of another gepant was prohibited. Subjects self-administered 1 dose of zavegepant 10 mg nasal spray per calendar day as needed to treat migraine attacks of any severity, up to 8 times per month, for 52 weeks. Months were defined as 4-week intervals. Safety assessments included adverse events (AEs), vital signs, ECG, nasal inspection, and clinical laboratory tests. Subjects who took ≥1 dose of zavegepant were included in the analysis.

Results

Of 608 subjects who entered the long-term treatment phase, 603 were treated with zavegepant 10 mg nasal spray. At baseline, the mean (SD) number of attacks per month was 5.0 (1.89), and 18.1% of treated subjects used preventive migraine medication. Treatment-emergent AEs reported in ≥ 5% of subjects (Figure) were dysgeusia (39.1%); nasal discomfort (10.3%); COVID-19 (7.5%); nausea (6.1%); nasal congestion and throat irritation (5.5% each); and back pain (5.3%). In total, 6.8% of subjects discontinued due to AEs; 1.5% discontinued due to dysgeusia. The majority of AEs (96.4%) were mild to moderate. Of the 7 serious AEs reported, none was considered related to treatment by the investigators. Aminotransferases >3x the upper limit of normal (ULN) occurred in 2.6% of subjects, none of whom had concurrent elevations in bilirubin >2x ULN. Subjects used a mean (SD) of 3.1 (1.6) zavegepant doses per month.

Conclusion

Favorable safety and tolerability profiles were observed with 1 year of open-label zavegepant 10 mg nasal spray for the acute treatment of migraine.