Axsome Therapeutics: FDA Approves Symbravo for Acute Treatment of Migraine

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The FDA has approved Symbravo (meloxicam and rizatriptan) for the acute treatment of migraine, according to a news release January 30, 2025 from developer Axsome Therapeutics.1

The novel oral multimechanistic medication combines the rapidly absorbed COX-2 preferential NSAID meloxicam and the 5-HT1 receptor agonist rizatriptan, considered one of the acute migraine therapies with the fastest onset of action. A proprietary technology developed by Axsome supports the rapid absorption of the NSAID component and sustains plasma half-life.1

Symbravo is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence.1

"Migraine is a debilitating condition that affects millions of Americans. Unfortunately, many patients still struggle to find an option that effectively treats their attacks and is both safe and well tolerated, which creates a great need for new migraine medicines," Stewart Tepper, MD, Clinical Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President of the New England Institute for Neurology and Headache, said in a news release. "Symbravo’s approval by the FDA provides a new medicine for physicians and patients that was designed to target key unmet needs in the migraine treatment space. The clinical data supporting its approval validates the additive benefit of Symbravo’s multi-mechanistic design and demonstrates its potential to make a meaningful difference for the migraine community.”1

Symbravo is thought to act by inhibiting calcitonin gene-related peptide (CGRP) release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization.1

In May 2022, the company received a complete response letter for its NDA submission of AXS-07, citing issues related to the chemistry, manufacturing, and controls considerations. At the time, the agency did not request any new clinical trials to be conducted.2

The original NDA, accepted for review in September 2021, was supported by data from 2 phase 3 randomized controlled clinical trials—the MOMENTUM trial and the INTERCEPT trial. Overall, the studies revealed a statistically significant elimination of migraine 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 at 2 hours post-dose (19.9%) compared with placebo (6.7%; P <.001) after dosing. Second, the absence of the most bothersome symptom (36.9%) compared with placebo (24.4%) was significant (P = .002).3

In April 2020, months after the initial readout of MOMENTUM, Axsome announced positive results from INTERCEPT. All told, the coprimary end points were also identical to MOMENTUM, with a statistically significantly greater percentage of patients achieving pain freedom at 2 hours compared with placebo (32.6% vs 16.3%, respectively; P = .002), as well as freedom from the most bothersome symptom (43.9% vs 26.7%, respectively; P = .003). AXS-07 also showed efficacy in preventing progression of migraine pain beyond mild intensity and significantly reducing the use of rescue medication, with freedom of pain progression occurring in 73.5% of AXS-07-treated patients compared with 47.4% of placebo patients between 2 and 24 hours post dose (P <.001).4

At the 2024 American Academy of Neurology Annual Meeting, investigators presented a pooled analysis of the MOMENTUM and INTERCEPT trials, with results showing that AXS-07 was effective at acutely treating migraine. In the pooled analysis, treatment with AXS-07 resulted in greater headache pain freedom (23% vs 11%; P <.001) and absence of the most bothersome symptom (39% vs 25%; P <.001) at 2 hours compared with placebo. Led by Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, 43% of AXS-07-treated patients had reduced rescue medication use through 24 hours vs 21% of those on placebo (P <.001). Notably, a higher rate of patients on the investigational agent returned to normal functioning in comparison with placebo starting at 1-hour post-dose.5

Symbravo is expected to be commercially available in the US within approximately 4 months, Axsome reported.1

It is estimated that over 39 million Americans suffer from migraine, and it is the leading cause of disability among neurological disorders in the US according to the American Migraine Foundation.6

References

1. Axsome Therapeutics Announces FDA Approval of SYMBRAVO® (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults. [News release]. Published January 30, 2025. Accessed January 30, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam.

2. Meglio M. Axsome Therapeutics: FDA accepts NDA resubmission for AXS-07 for acute treatment of migraine. Patient Care Online. Published September 16, 2024. Accessed January 30, 2025. https://www.patientcareonline.com/view/axsome-therapeutics-fda-accepts-nda-resubmission-for-axs-07-for-acute-treatment-of-migraine

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 January 30, 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 AXS-07 achieves both co-primary endpoints and prevents migraine pain progression in the INTERCEPT phase 3 trial in the early treatment of migraine. News release. Axsome Therapeutics. April 6, 2020. Accessed January 30, 2025. https://www.finance.yahoo.com/news/axsome-therapeutics-announces-axs-07-100010869.html

5. Tepper S. Lipton R, Chhabra A, Streicher C, Parks G, Tabuteau H. Combined efficacy and safety of AXS-07 (MOSEICTM meloxicam and rizatriptan) in two phase 3 clinical trials. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. Abstract 00519

6. American Migraine Foundation. 2023. Accessed January 30, 2025.