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FDA approves AXS-07 (meloxicam and rizatriptan) for the acute treatment of migraine in adults

On January 30, 2025, the U.S. Food and Drug Administration (FDA) approved AXS-07, a novel, oral medication for the acute treatment of migraine with or without aura in adults. This landmark approval marks a significant advancement in migraine care, offering patients a new, multi-mechanistic option to address debilitating symptoms.1

Mechanism of action

AXS-07 combines rizatriptan, a serotonin (5-HT1B/D) receptor agonist, and meloxicam, a non-steroidal anti-inflammatory drug (NSAID), to provide a dual mechanism of action. Meloxicam exerts its therapeutic effect by inhibiting cyclooxygenase-2 (COX-2) to reverse central sensitization, while rizatripan inhibits the release of calcitonin gene-related peptide (CGRP), a key mediator in migraine pathophysiology. This reverses CGRP-mediated vasodilation, reducing neuroinflammation and blocking pain signal transmission to alleviate acute migraine symptoms.2 By targeting several pathways involved in migraine onset and progression, AXS-07 aims to improve treatment outcomes, particularly for patients who have had inadequate responses to standard therapies.

Pivotal trials

The approval of AXS-07 was supported by data from two Phase III randomized controlled trials – MOMENTUM (NCT03896009) and INTERCEPT (NCT04163185).

MOMENTUM evaluated 1,594 patients with moderate to severe migraines and a history of inadequate response to prior treatments. Participants were randomized to receive AXS-07, rizatriptan, meloxicam, or placebo.3 In the INTERCEPT study, 302 patients were randomized to receive a single dose of AXS-07 or placebo at the earliest onset of mild migraine pain.4 A pooled analysis from MOMENTUM and INTERCEPT was presented at the 2024 American Academy of Neurology (AAN) Annual Meeting. The findings underscored the efficacy of AXS-07, revealing pain freedom (PF) at two hours of 23% in patients treated with AXS-07 versus 11% with placebo (p<0.001). Patients treated with AXS-07 experienced greater sustained PF compared with placebo, with significantly higher rates between two and 24 hours (18% versus 8%, p<0.001) and at 48 hours (16% versus 7%, p<0.001). They also required less rescue medication within the first 24 hours (43% versus 21%, p<0.001). Additionally, a greater proportion of AXS-07-treated participants returned to normal functioning as early as one hour after dosing compared with those receiving placebo.5 These findings demonstrate the superior efficacy of AXS-07 compared with both placebo and its individual components, meloxicam and rizatriptan.

Safety of AXS-07

In the pooled analysis of the MOMENTUM and INTERCEPT trials, treatment-emergent adverse events (TEAEs) were observed in 12.7% of patients receiving AXS-07, compared with 6.6% in the placebo group. The most frequently reported TEAEs among those treated with AXS-07 included nausea, somnolence, and dizziness.5 The MOVEMENT trial (NCT04068051) aimed to evaluate the long-term safety of AXS-07 and included 706 patients who had received this treatment intermittently for up to 12 months and at least twice per month. In this trial, AXS-07 was well tolerated, with nausea, dizziness, and vomiting being the most reported adverse events over 12 months.6

Conclusion

The approval of AXS-07 by the FDA represents an important step forward for individuals living with migraines. By offering a multi-mechanistic approach to treatment, AXS-07 has the potential to address unmet needs, particularly for patients who do not respond to existing therapies.

Written by Hannah Elkheir

Reviewed by Raffaella Facchini

References

  1. Axsome Therapeutics. Axsome Therapeutics Announces FDA Approval of SYMBRAVO® (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults. [Press Release]. 30th January 2025. Accessed 31st January 2025.
  2. Ong JJY, De Felice M. Migraine treatment: current acute medications and their potential mechanisms of action. Neurotherapeutics. April 2018;15(2):274-290.
  3. Jones A, Tepper S, Lipton R, Tabuteau H. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: results from the MOMENTUM Phase 3, randomized, double-blind, active- and placebo-controlled trial. Neurology. May 3, 2022;98(18_supplement).
  4. Jones A, Tepper S, Lipton R, Tabuteau H. Efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: results from the INTERCEPT Phase 3, randomized, double-blind, placebo-controlled trial. Neurology. May 3, 2022;98(18_Supplement).
  5. Tepper S, Lipton R, Chhabra A, et al. Combined efficacy and safety of AXS-07 (MoSEIC meloxicam and rizatriptan) in two Phase 3 clinical trials. Neurology. April 9, 2024;102(17_Supplement_1).
  6. Jones A, Tabuteau H. Long-term efficacy and safety of AXS-07 (MoSEIC meloxicam-rizatriptan) for the acute treatment of migraine: results from the MOVEMENT Phase 3 trial. Neurology. May 3, 2022;98(18_Supplement).