The Rationale Behind Recently Approved AXS-07 Combination Therapy for Migraine: Stewart Tepper, MD

WATCH TIME: 6 minutes

"What we're really after clinically is ‘one and done.’ We want to treat and have [the patient] pain-free in 2 hours, without significant [adverse] effects most of the time, and without a recurrence of the headache.”

Combination therapies in migraine management involve using 2 or more treatments, either acute or preventive, together to address different aspects of the migraine process. Common acute treatments, such as nonsteroidal anti-inflammatory drugs and triptans, target distinct mechanisms in the inflammatory and neural pathways of migraines. When used together, these treatments provide incremental benefits. For instance, the combination of sumatriptan and naproxen sodium has proven effective in treating migraines. Other fixed combinations include acetaminophen/aspirin/caffeine and combinations containing butalbital.¹

Research supports the efficacy of combination therapy, with 62% of studies showing improved outcomes compared with monotherapy. Additionally, 90% of studies reported no significant increase in adverse effects, suggesting that combination therapies can enhance efficacy without compromising tolerability. However, some studies did not demonstrate superior benefits, underlining the need for further research to identify which drug combinations are most effective.² The recent FDA approval of AXS-07 (Symbravo; Axsome Therapeutics), a combination therapy of meloxicam and rizatriptan, highlighted the potential for tailored, effective migraine treatment, offering a new option for adults with migraine with or without aura.³

Following this news, Stewart Tepper, MD, a professor of neurology at the Geisel School of Medicine at Dartmouth, sat down in a recent interview with NeurologyLive^® to further share his perspective on the approval. Tepper, who also serves as the vice president of the New England Institute for Neurology and Headache, talked about how this newly approved combination therapy may improve outcomes compared with monotherapy medications on their own.In the conversation, he also spoke about the challenges healthcare providers may face in ensuring patients follow combination therapy protocols. In addition, he spoke on how pharmacokinetic properties of new formulations like AXS-07 might contribute to more rapid and sustained migraine relief.

REFERENCES
1. Pellesi L, Garcia-Azorin D, Rubio-Beltrán E, et al. Combining treatments for migraine prophylaxis: the state-of-the-art. J Headache Pain. 2024;25(1):214. Published 2024 Dec 5. doi:10.1186/s10194-024-01925-w
2. Lipton RB, Ailani J, Blumenfeld AM. What Is Combination Treatment in Migraine? Moving Toward a Uniform Definition of a Familiar Principle. Neurol Ther. 2024;13(6):1535-1540. doi:10.1007/s40120-024-00669-8
3. 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 February 4, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam

Editor’s note: Tepper has received advisory fees from numerous pharmaceutical and healthcare organizations, including AbbVie, Amgen, Axsome Therapeutics, Eli Lilly, Lundbeck, Novartis, Pfizer, Teva, and others. He has received honoraria for lectures and continuing medical education from institutions such as the American Academy of Neurology, the American Headache Society, Medscape, and multiple medical education providers. Additionally, he has received research funding from Aeon, AbbVie, Eli Lilly, Lundbeck, Neurolief, Pfizer, and Suven. Travel support has been provided by AbbVie, the American Headache Society, Diamond Headache Clinic, Eli Lilly, and Pfizer.