Symbravo Outperformed Gepants Across Multiple Acute Migraine End Points in Network Meta-Analysis

A network meta-analysis presented at the 68th Annual Scientific Meeting of the American Headache Society found that Symbravo (meloxicam 20 mg/rizatriptan 10 mg; Axsome Therapeutics, New York, NY) was favored over the gepants rimegepant, ubrogepant, and zavegepant across several efficacy measures for the acute treatment of migraine. Symbravo was associated with greater odds of achieving 2-hour pain freedom, sustained pain freedom from 2 to 24 hours, improved functional outcomes, and lower use of rescue medication compared with the comparator gepants.

The analysis incorporated data from the phase 3 MOMENTUM trial (NCT03896009) and 7 placebo-controlled phase 3 studies evaluating rimegepant, ubrogepant, or zavegepant. Investigators conducted a fixed-effects Bayesian network meta-analysis using placebo as the common comparator. Outcomes included 2-hour pain relief and pain freedom, sustained pain relief and pain freedom from 2 to 24 hours, absence of the most bothersome symptom, ability to perform normal activities at 2 hours, and use of rescue medication between 2 and 24 hours.

Pain Freedom and Rescue Medication Findings

• Compared with rimegepant, ubrogepant, and zavegepant, Symbravo was associated with higher odds of achieving 2-hour pain freedom (OR, 1.96; 1.98; and 2.07, respectively).
• Symbravo also demonstrated higher odds of sustained 2- to 24-hour pain freedom versus rimegepant (OR, 1.66; 95% CI, 0.85 to 3.51), ubrogepant (OR, 2.07; 95% CI, 1.04 to 4.46), and zavegepant (OR, 2.25; 95% CI, 1.14 to 4.83).
• Sustained pain relief from 2 to 24 hours favored Symbravo over zavegepant (OR, 1.66).
• Rescue medication use between 2 and 24 hours was lower with Symbravo, particularly in comparison with zavegepant (OR, 0.47).
• Numerical trends also favored Symbravo for absence of the most bothersome symptom and ability to perform normal activities at 2 hours.

Investigators concluded that the network meta-analysis favored Symbravo over the 3 approved gepants evaluated for acute migraine treatment. The findings suggest the potential for Symbravo to provide advantages in achieving both early and sustained pain freedom outcomes, particularly in patients who have experienced inadequate response to prior acute therapies. As an indirect comparison, however, the results should be interpreted within the limitations of network meta-analysis methodology, and no head-to-head randomized trials were included.

Source

Nahas SJ, Zhao Y, Graham C, et al. Comparative efficacy of Symbravo versus gepants for acute treatment of migraine: a network meta-analysis. Presented at: American Headache Society Annual Scientific Meeting; June 4-7, 2026; Orlando, FL. Abstract T24.