AXS-07 Outperforms Other CGRP-Targeting Gepants in Meta-Analysis

Findings from a new meta-analysis revealed that AXS-07 (Symbravo; Axsome Therapeutics), a recently approved therapy for acute migraine, was more effective in providing sustained benefits than previously approved gepants such as rimegepant (Nurtec ODT; Pfizer), ubrogepant (Ubrelvy; AbbVie), and zavegepant (Zavzpret; Pfizer).¹

Presented at the 2025 American Academy of Neurology (AAN) Annual Meeting, held April 5-9, in San Diego, California, the analysis included the phase 3 MOMENTUM study (NCT03896009) for which AXS-07 was approved on, as well as 7 placebo-controlled phase 3 trials of the comparator drugs. Led by Stephanie J. Nahas, MD, MSEd, associate director of the Headache Fellowship Program at Thomas Jefferson University, the analysis observed several outcomes, including 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.

All told, compared with rimegepant, Ubrogepant, and zavegepant, those on AXS-07 were more likely to achieve 2-hour pain relief (OR, 1.06 [95% CI, 0.73-1.53]; OR, 1.10 [95% CI, 0.75-1.61]; OR, 1.33 [95% CI, 0.91-1.96]) and 2-hour pain freedom (OR, 1.96 [95% CI, 1.07-3.78]; OR, 1.98 [95% CI, 1.07-3.89]; OR, 2.07 [95% CI, 1.13-4.06]). AXS-07, which was approved in late January, also outperformed these therapies on outcomes of sustained 2–24-hour pain relief (OR, 1.11 [95% CI, 0.77-1.62]; OR, 1.02 [95% CI, 0.69-1.52]; OR, 1.66 [95% CI, 1.13-2.45]).

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AXS-07, a novel therapy, works by suppressing calcitonin gene-related peptide (CGRP) release, counteracting CGRP-induced vasodilation, and reducing neuroinflammation, pain signal transmission, and central sensitization. Comprising meloxicam and rizatriptan, the agent leverages Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology to enhance absorption speed and extend plasma half-life.

Additional data from the meta-analysis revealed that AXS-07-treated patients demonstrated greater absence of MBS (vs rimegepant: OR, 1.15 [95% CI, 0.78-1.73]; vs Ubrogepant: OR, 1.11 [95% CI, 0.73-1.69]; vs zavegepant: OR, 1.26 [95% CI, 0.84-1.92]) and improved ability to perform normal activities at 2 hours (OR, 1.03 [95% CI, 0.68-1.58]; OR, 1.18 [95% CI, 0.77-1.82]; OR, 1.16 [95% CI, 0.75-1.81]. Furthermore, in comparison with the other gepants, AXS-07 led to reduced use of migraine medications from 2-24 hours (OR, 0.84 [95% CI, 0.57-1.23]; OR, 0.68 [95% CI, 0.43-1.10]; OR, 0.47 [95% CI, 0.32-0.71]).

After years of back and forth with the FDA, the agency finally approved AXS-07 in late January based on findings from MOMENTUM, as well as INTERCEPT (NCT04163185), another phase 3 randomized controlled trial. Overall, both studies revealed a statistically significant elimination of pain with AXS-07 compared with placebo and active controls. In MOMENTUM, AXS-07 met its coprimary end points with statistical significance, first showing a greater percentage of patients achieving pain freedom (19.9%) compared with placebo (6.7%; P <.001) 2 hours after dosing. Second, the absence of the MBS (36.9%) compared with placebo (24.4%) was significant (P = .002).^2,3

Weeks after the drug’s approval, data from the phase 3 EMERGE trial (NCT05550207) showed that AXS-07 has an impact on patients with migraine who’ve previously failed oral CGRP inhibitors. In the study, the therapy met its primary end point, demonstrating greater treatment response relative to prior CGRP inhibitors, as assessed by changes in Migraine Treatment Optimization Questionnaire total score (5.2 vs 2.8; P <.001) over the 8-week treatment period.⁴

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REFERENCES
1. Nahas SJ, Zhao Y, Graham CN, Erbe A, Blumenfeld A. Comparative Efficacy of AXS-07 vs. Gepants for Acute Treatment of Migraine: A Network Meta-Analysis. Presented at: 2025 AAN Annual Meeting; April 5-9; ABSTRACT 002730.
2. Axsome Therapeutics Announces FDA Approval of SYMBRAVO® (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults. News Release. Axsome Therapeutics. Published January 30, 2025. Accessed April 8, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam
3. Axsome Therapeutics Announces AXS-07 Achieves Co-Primary and Key Secondary Endpoints in MOMENTUM Phase 3 Migraine Trial in Patients with History of Inadequate Response. News release. Axsome Therapeutics. December 30, 2019. Accessed April 8, 2025. https://www.biospace.com/article/releases/axsome-therapeutics-announces-axs-07-achieves-co-primary-and-key-secondary-endpoints-in-momentum-phase-3-migraine-trial-in-patients-with-history-of-inadequate-response
4. Axsome Therapeutics Announces SYMBRAVO® (meloxicam and rizatriptan) Achieves Primary Endpoint in the EMERGE Phase 3 Trial in Migraine Patients Experiencing Inadequate Response to Oral CGRP Inhibitors. News release. Axsome Therapeutics. February 24, 2025. Accessed April 8, 2025. https://www.globenewswire.com/news-release/2025/02/24/3031008/33090/en/Axsome-Therapeutics-Announces-SYMBRAVO-meloxicam-and-rizatriptan-Achieves-Primary-Endpoint-in-the-EMERGE-Phase-3-Trial-in-Migraine-Patients-Experiencing-Inadequate-Response-to-Oral.html