Clinical Perspective on Newly Approved Combination Therapy for Migraine: Richard B. Lipton, MD

WATCH TIME: 5 minutes

"In treatment-refractory patients, the combination product produces excellent 2-hour pain freedom and freedom from the most bothersome symptom, corresponding to an early onset of action but also sustained benefits."

AXS-07 (Symbravo; Axsome Therapeutics), a novel agent consisting of meloxicam and rizatriptan, 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. In late January, the FDA approved AXS-07 as a new acute treatment of migraine with or without aura in adults, months after the agency accepted the company’s resubmission of its new drug application (NDA) in September 2024. The company noted that it expects AXS-07 to be commercially available in the United States in approximately 4 months.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 (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.^3,4 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 a recent interview with NeurologyLive^®, principal investigator of the MOMENTUM study Richard B. Lipton, MD, professor of neurology and director of the Montefiore Headache Center at Albert Einstein College of Medicine, discussed his initial reaction to the FDA approval of the new migraine treatment. He shared his excitement about how the combination of rizatriptan and meloxicam will change the landscape of migraine care, particularly for patients with poor responses to existing therapies. Lipton also highlighted key findings from MOMENTUM, noting the impressive efficacy of the treatment in refractory patients and its potential to drive positive outcomes for both clinical practice and future drug development.

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 February 3, 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 February 3, 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 February 3, 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 February 3, 2025. https://www.finance.yahoo.com/news/axsome-therapeutics-announces-axs-07-100010869.html

Editor's Note: Lipton has received research support from the National Institutes of Health, the FDA, and the National Headache Foundation. He serves as consultant, advisory board member, or has received honoraria or research support from AbbVie/Allergan, Amgen, Biohaven, Dr. Reddy's Laboratories (Promius), electroCore, Eli Lilly and Company, GlaxoSmithKline, Lilly, Lundbeck, Merck, Novartis, Pfizer, Teva, Vector, and Vedanta Research. He receives royalties from Wolff's Headache, 8th edition (Oxford University Press, 2009) and Informa. He holds stock/options in Axon, Biohaven, Cooltech, and Mainistee.