What is the efficacy of intranasal zavegepant compared with oral rimegepant (Nurtec ODT) for acute abortive treatment of migraine in adults?

Efficacy of Zavegepant vs Nurtec for Abortive Migraine Therapy

Both zavegepant nasal spray and rimegepant (Nurtec ODT) demonstrate comparable efficacy for acute migraine treatment, with zavegepant offering a slight advantage in speed of onset due to intranasal delivery, while rimegepant provides the unique benefit of dual indication for both acute and preventive therapy.

Direct Efficacy Comparison

Pain Freedom at 2 Hours (Primary Endpoint)

• Zavegepant 10 mg nasal spray achieves pain freedom in 24% of patients at 2 hours (NNT = 11), compared to 15% with placebo 1
• Rimegepant 75 mg ODT achieves pain freedom with an NNT of 9 at 2 hours, demonstrating slightly superior efficacy on this endpoint 2
• Both agents significantly outperform placebo on freedom from most bothersome symptom at 2 hours: zavegepant 40% vs placebo 31% (risk difference 8.7 percentage points) 1, while rimegepant shows comparable benefit 3

Clinical Positioning in Guidelines

• The 2023 VA/DoD guidelines assign both ubrogepant and rimegepant a "weak for" recommendation for acute migraine treatment, with systematic reviews demonstrating moderately robust and clinically significant effects (NNT of 13 for pain freedom at 2 hours for gepants reviewed) 4
• Gepants are positioned as second-line therapy after NSAIDs and triptans, specifically recommended when triptans are contraindicated, ineffective, or poorly tolerated 5

Key Differentiating Features

Route of Administration Advantages

• Zavegepant's intranasal delivery provides faster onset of action compared to oral formulations, making it particularly useful for patients with rapid progression to peak intensity, severe nausea/vomiting, or gastroparesis 6
• Rimegepant's orally disintegrating tablet (ODT) formulation offers convenience without requiring water, though absorption still depends on gastrointestinal function 3

Dual Indication Advantage of Rimegepant

• Rimegepant is the only gepant approved for both acute treatment (as needed) and preventive treatment (every other day), providing flexibility for patients requiring both approaches 3
• For prevention, rimegepant reduces monthly migraine days by 0.8 days, though the 2023 VA/DoD guidelines rated this reduction as not clinically significant and assigned a "neither for nor against" recommendation 4

Safety and Tolerability Profile

Adverse Events

• Zavegepant's most common adverse events are dysgeusia (21% vs 5% placebo), nasal discomfort (4% vs 1%), and nausea (3% vs 1%), with most events mild to moderate and self-resolving 1
• Rimegepant demonstrates a favorable tolerability profile with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials, and minimal potential for medication-overuse headache 3
• Neither agent shows vasoconstrictor activity, making both safe alternatives for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease where triptans are contraindicated 2, 6

Treatment Algorithm for Selection

Choose Zavegepant When:

• Patient experiences attacks with sudden onset requiring rapid relief 6
• Significant nausea or vomiting is present at attack onset, limiting oral medication absorption 6
• Patient has gastroparesis or other conditions affecting oral medication absorption 6
• Patient prefers non-oral administration 6

Choose Rimegepant When:

• Patient requires both acute and preventive therapy (can use same medication for both indications) 3
• Patient prefers oral administration but wants convenience of ODT formulation 3
• Cost considerations favor rimegepant (dual indication may provide better value) 3

Critical Frequency Limitation for Both Agents

• Limit all acute migraine medications, including both zavegepant and rimegepant, to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache 4, 5
• If acute treatment is needed more than twice weekly, initiate preventive therapy immediately 5

Common Pitfall to Avoid

• Do not use gepants as first-line therapy before trying NSAIDs or triptan-NSAID combinations, as guidelines position them as second-line options after failure of or contraindications to first-line agents 5
• Do not assume failure of one gepant predicts failure of another, though head-to-head studies comparing zavegepant and rimegepant are lacking 6