FDA Approves Axsome Therapeutics’ AXS-07 for Migraine Treatment

Months after the FDA accepted Axsome Therapeutics’ resubmission of its new drug application (NDA) in September 2024, the agency has approved AXS-07, an oral, rapidly absorbed, multi-mechanistic agent, as a new acute treatment of migraine with or without aura in adults. Marketed as Symbravo, the company noted that it anticipates AXS-07 to be commercially available in the United States in approximately 4 months.

AXS-07, a novel agent, 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. The agent, which consists of meloxicam and rizatriptan, is enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in faster absorption and longer plasma half-life.

"In terms of use in clinical practice, we want to treat our patients with the simplest, most effective acute treatments that we're able to offer them. So, you would not use a combination triptan and non-steroidal product in a patient whose treatment needs were fully met, either by a triptan alone or by a non-steroidal anti-inflammatory alone," Richard B. Lipton, MD, professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, told NeurologyLive^® in a recent interview. "In fact, the design for individuals with unmet needs on single, monotherapy acute treatments was specifically a reflection of the fact that those are the patients who need combination therapy. I think that's something most prescribers would do and should do."

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 (NCT03896009) and the INTERCEPT trial (NCT04163185). 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 (19.9%) compared with placebo (6.7%; P <.001) 2 hours after dosing. Second, the absence of the most bothersome symptom (36.9%) compared with placebo (24.4%) was significant (P = .002).³

In MOMENTUM, 1594 patients with migraine were randomly assigned 2:2:2:1 to AXS-07, 10-mg rizatriptan, MoSEIC 20-mg meloxicam, or placebo, to treat a single migraine attack of moderate or severe intensity. INTERCEPT included 302 patients with migraine who were randomly assigned to either AXS-07 (n = 152) or placebo (n = 150) at the earliest onset of migraine pain.

“It's always good when a new treatment is approved for migraine. This particular combination tablet is something that I've been working on as an investigator for years, so I'm delighted that it got approved, and I'm looking forward to when it becomes available in the next several months for patients for the acute treatment of migraine," Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and vice president of the New England Institute for Neurology and Headache, told NeurologyLive in a recent interview. "The hope is that as we educate practitioners, the understanding of why combining an [nonsteroidal anti-inflammatory drugs] with a triptan should provide additional benefit in the acute treatment of migraine for patients will become more and more clear, and that is my hope for the future."

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 compared with placebo (32.6% vs 16.3%, respectively; P = .002) at 2 hours post dose, 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

“Today’s approval of SYMBRAVO marks an important milestone for the migraine community by providing a rationally designed novel acute treatment for this debilitating condition. Migraine attacks strike without warning, and disrupt the lives of estimated more than 39 million patients in the U.S. alone," Herriot Tabuteau, MD, chief executive officer at Axsome Therapeutics, said in a statement.¹ "SYMBRAVO provides patients and clinicians an important new option which can quickly stop a migraine attack, keep it away, and allow patients to resume their normal activities, with just a single dose. SYMBRAVO demonstrates Axsome’s commitment to developing and delivering differentiated new treatments to improve the lives of patients living with difficult to treat central nervous system disorders.”

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

“Migraine is one of the most misunderstood and stigmatized neurological diseases, despite the fact that one in four households in the U.S. includes someone living with it. This widespread lack of understanding creates unnecessary barriers for individuals seeking proper diagnosis, care, and treatment," Susan Doughty, executive director of the Coalition for Headache and Migraine Patients (CHAMP), said in a statement.¹ "CHAMP, alongside our 20 plus dedicated coalition organizations and patient advocates, is committed to empowering the migraine community by providing education, reducing stigma, and advocating for fair and equitable access to treatment options. The approval of SYMBRAVO as a new acute treatment for migraine is an important step forward, offering a new option for people seeking relief. We also see this moment as an opportunity to continue to shine a bright light on migraine, fostering greater awareness and helping to dismantle the stigma that so often surrounds this disease.”

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. Axsome Therapeutics. 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. Axsome Therapeutics Receives FDA Complete Response Letter for New Drug Application for AXS-07 for the Acute Treatment of Migraine. News release. Axsome Therapeutics. May 2, 2022. Accessed January 30, 2025 https://www.prnewswire.com/news-releases/axsome-therapeutics-receives-fda-complete-response-letter-for-new-drug-application-for-axs-07-for-the-acute-treatment-of-migraine-301537093.html
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