OBJECTIVE: To compare the efficacy of AXS-07 with gepants (rimegepant, ubrogepant, zavegepant) approved for acute migraine treatment in the United States using a network meta-analysis (NMA).
BACKGROUND: AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine to treat migraine, consisting of MoSEICTM (Molecular Solubility Enhanced Inclusion Complex) meloxicam and rizatriptan. The MOMENTUM (NCT0389600) phase 3 randomized, double-blind, single-dose, placebo-controlled trial demonstrated the efficacy and safety of AXS-07 in the acute treatment of migraine, with or without aura, in adults with a history of inadequate response to prior treatments. Methods: The analysis included MOMENTUM and 7 placebo-controlled Phase 3 trials of the comparator drugs. A fixed effects Bayesian NMA was conducted focusing on 2-hour and 2-24 hour pain relief and pain freedom, absence of most bothersome symptoms (MBS), ability to perform normal activities at 2 hours, and use of rescue medications from 2-24 hours. Results were summarized with odds ratios (OR) and 95% credible intervals (CIs).
RESULTS: Compared to rimegepant, ubrogepant, and zavegepant, participants treated with AXS-07 were more likely to achieve 2-hour pain relief (OR [95% CI]: 1.06 [0.73-1.53], 1.10 [0.75-1.61], 1.33 [0.91-1.96]), 2-hour pain freedom (1.96 [1.07-3.78], 1.98 [1.07-3.89], 2.07 [1.13-4.06]), sustained 2-24 hour pain relief (1.11 [0.77-1.62], 1.02 [0.69-1.52], 1.66 [1.13-2.45]), and sustained 2-24 hour pain freedom (1.66 [0.85-3.51], 2.07 [1.04-4.46], 2.25 [1.14-4.83]). AXS-07 also showed greater absence of MBS (1.15 [0.78-1.73], 1.11 [0.73-1.69], 1.26 [0.84-1.92]), improved ability to perform normal activities at 2 hours (1.03 [0.68-1.58], 1.18 [0.77-1.82], 1.16 [0.75-1.81]), and reduced use of rescue medications from 2–24 hour (0.84 [0.57-1.23], 0.68 [0.43-1.10], 0.47 [0.32-0.71]).
CONCLUSIONS: The NMA favors AXS-07 over rimegepant, ubrogepant, and zavegepan for acute migraine. AXS-07 is particularly effective in achieving 2-hour and 2-24 hour sustained pain freedom, offering a promising therapeutic alternative for patients with inadequate response to prior treatments.
