Zavegepant Intranasal
(2023)Objective
To evaluate the efficacy and safety of zavegepant 10 mg intranasal spray compared to placebo for the acute treatment of migraine in adults
Study Summary
• Met co-primary endpoints of pain freedom (24% vs 15%, P<0.0001) and freedom from most bothersome symptom (40% vs 31%, P=0.0012) at 2 hours post-dose
• Demonstrated pain relief as early as 15 minutes with sustained relief up to 48 hours
Intervention
Zavegepant 10 mg intranasal spray versus placebo
Inclusion Criteria
Adults with migraine experiencing 2-8 moderate or severe migraine attacks per month
Study Design
Arms: 2 arms: Zavegepant 10 mg intranasal spray vs placebo
Patients per Arm: Approximately 703 per arm (total 1,405)
Outcome
• Freedom from most bothersome symptom at 2 hours: 40% zavegepant vs 31% placebo (P=0.0012)
• Pain relief beginning at 15 minutes and sustained through 48 hours
• Most common adverse events: dysgeusia (20.5%), nasal discomfort (3.7%), nausea (3.2%)
Bottom Line
Zavegepant 10 mg intranasal spray demonstrated superiority over placebo for acute treatment of migraine, achieving significantly higher rates of pain freedom and freedom from most bothersome symptom at 2 hours post-dose, with pain relief beginning as early as 15 minutes and lasting up to 48 hours. The treatment was well tolerated with no serious adverse events.
Major Points
- First Phase 3 trial of a non-oral CGRP receptor antagonist for acute migraine treatment
- Met both co-primary endpoints: pain freedom at 2 hours (24% vs 15%, P<0.0001) and freedom from most bothersome symptom at 2 hours (40% vs 31%, P=0.0012)
- Demonstrated rapid onset of pain relief at 15 minutes with sustained benefits through 48 hours
- Well tolerated with dysgeusia (altered taste) being the most common adverse event (20.5% vs 4.7% placebo)
- No serious adverse events or hepatotoxicity signals identified
- Zavegepant is a third generation, high affinity, selective small molecule CGRP receptor antagonist
Study Design
- Study Type
- Randomized, placebo-controlled, double-blind trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 1405
- Follow-up
- 48 hours post-dose
- Countries
- United States
Primary Outcome
Definition: Co-primary endpoints: Pain freedom at 2 hours post-dose and freedom from most bothersome symptom at 2 hours post-dose
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 15% pain freedom, 31% freedom from MBS | 24% pain freedom, 40% freedom from MBS | - | P<0.0001 for pain freedom; P=0.0012 for freedom from MBS |
Limitations & Criticisms
- One secondary endpoint (return to normal function at 15 minutes) did not reach significance, preventing formal testing of remaining endpoints per hierarchical analysis plan
- Exclusion criteria not detailed in the press release
- Limited follow-up duration for long-term safety assessment
- No comparison to active comparators (e.g., triptans)
- Baseline characteristics not fully detailed by treatment arm
Citation
Published February 16, 2023 in The Lancet Neurology