Zavegepant Nasal Spray Improves Two-Hour Migraine Outcomes

Key Takeaways

• Among adults treating a single moderate or severe migraine attack in Chinese Mainland, South Korea, and Taiwan, two-hour pain freedom was significantly more frequent with zavegepant than placebo.
• Freedom from the patient-selected most bothersome symptom at two hours was also significantly more frequent with zavegepant than placebo.
• Six of eight key secondary endpoints reached statistical significance, including early and sustained pain relief.
• Overall adverse-event incidence was generally comparable with placebo, and investigators described hepatic safety as comparable.

During a moderate or severe migraine attack, eliminating pain and eliminating the accompanying symptom a patient finds most bothersome are distinct treatment goals. A patient may still experience nausea or sensitivity to light or sound after headache pain subsides, or may have pain after another symptom resolves. Intranasal zavegepant was compared with placebo for both outcomes after treatment of a single attack.

Investigators in Yu and colleagues’ phase 3 zavegepant trial in The Journal of Headache and Pain conducted a randomized, double-blind, placebo-controlled, parallel-group study at sites in Chinese Mainland, South Korea, and Taiwan. Adults with an established migraine history were assigned equally to zavegepant 10 mg nasal spray or placebo to treat one attack of moderate or severe intensity. The study included 1,346 efficacy-evaluable participants, with similar numbers in each group. The co-primary measures were freedom from pain and freedom from a patient-selected symptom present before dosing, assessed two hours after treatment. Investigators assessed safety through adverse events and laboratory testing.

At two hours, 23.2% of zavegepant recipients were pain-free, compared with 14.1% of placebo recipients. The investigators reported a treatment difference of 9.2 percentage points (p < 0.0001). Pain freedom required an absence of pain at the assessment, rather than a reduction in pain intensity.

At the same assessment, 52.7% of zavegepant recipients were free from their prespecified most bothersome symptom, compared with 39.9% of placebo recipients. The reported treatment difference was 12.8 percentage points (p < 0.0001). Significant secondary findings also included pain relief soon after dosing and sustained pain relief later in the observation period.

Overall adverse-event incidence was generally comparable with placebo, and investigators characterized hepatic safety as comparable between groups. The observations concern treatment of one attack at sites in Chinese Mainland, South Korea, and Taiwan. They do not establish outcomes with repeated use or in a North American cohort.

Yu and colleagues concluded that zavegepant 10 mg nasal spray was more effective than placebo on the studied acute migraine endpoints. They described it as well tolerated among adults treated for one moderate or severe attack.

Clinician Questions

Which symptoms qualified as the most bothersome symptom for zavegepant in acute migraine?

For adults treating a moderate or severe migraine attack with zavegepant nasal spray or placebo, the symptom had to be present before dosing and was selected from nausea, photophobia, or phonophobia. Freedom meant the selected symptom was absent at the postdose assessment.

How severe were adverse events during single-attack zavegepant nasal spray treatment for migraine?

In the trial of zavegepant nasal spray versus placebo for one moderate or severe migraine attack in Asian adults, investigators described most adverse events as mild, judged unrelated to the assigned intervention, and resolved without treatment.