FDA Approves Meloxicam and Rizatriptan (Symbravo) for Acute Migraine With or Without Aura

The US Food and Drug Administration (FDA) approved meloxicam and rizatriptan (Symbravo), formerly AXS-07, for acute migraine with or without aura, according to an announcement by Axsome Therapeutics on January 30, 2025.1

Backed by positive data from the MOMENTUM and INTERCEPT Phase 3 trials, combination meloxicam and rizatriptan demonstrated superiority over placebo in relieving migraine symptoms.2

“A significant proportion of migraine patients experience inadequate efficacy with currently available acute treatments, leading to even greater suffering, and an increased risk of worsening of migraine pain and attack frequency," said Richard B. Lipton, MD, professor of Neurology and director of the Montefiore Headache Center at the Albert Einstein College of Medicine.1 "Results of multiple clinical trials demonstrate that [meloxicam and rizatriptan] can provide rapid and long-lasting freedom from migraine pain, whether treatment is taken early in the attack while the pain is mild, or later in the attack when the pain may be severe. The approval of [meloxicam and rizatriptan] is a long-awaited and much welcomed advancement for clinicians and our patients, providing a new, meaningful treatment option.”1

The approval of this New Drug Application (NDA) follows a Complete Response Letter (CRL) from May 2022, addressing manufacturing concerns but not requiring additional clinical trials.1 Meloxicam and rizatriptan is a novel treatment for acute migraine, using Axsome’s MoSEIC technology to enable rapid absorption and longer plasma half-life.

INTERCEPT, a double-blind, placebo-controlled trial, included 302 adult patients randomized 1:1 to receive a single dose of meloxicam and rizatriptan (20 mg meloxicam/10 mg rizatriptan) or placebo to treat a migraine attack.3 Participants were given meloxicam and rizatriptan or a placebo at the earliest sign of migraine pain when pain intensity was mild. The trial met all co-primary endpoints of pain freedom and freedom from the most bothersome symptom at 2 hours.

Just 2 hours after dosing, a significantly greater percentage of patients achieved pain freedom compared with placebo (32.6% vs 16.3% vs; P = .002), as well as freedom from the most bothersome symptom (43.9% vs 26.7%; P = .003). After 2 – 24 hours of taking the dose, freedom of pain progression occurred in 73.5% of patients on meloxicam and rizatriptan compared with 47.4% on placebo (P < .001).

Participants on meloxicam and rizatriptan achieved pain freedom and most bothersome symptom freedom as early as 30 minutes, with significant migraine pain freedom at 90 minutes (P = .003). Fewer patients on meloxicam and rizatriptan (15.3%) needed rescue medication than patients on placebo (42.4%) over 24 hours (P < .001).

Meloxicam and rizatriptan was generally safe and well tolerated with no reported serious adverse events. The most common adverse events were somnolence, dizziness, and paresthesia, which had occurred in < 5% of participants.

“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," said 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. "[Meloxicam and rizatriptan] 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.”

References

1. Axsome Therapeutics, Inc. Axsome Therapeutics announces FDA approval of SYMBRAVO® (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults. Axsome Therapeutics, Inc. 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. Campbell, P. 5 FDA Decisions to Watch in Q1 2025. HCPLive. December 26, 2024. https://www.hcplive.com/view/5-fda-decisions-to-watch-in-q1-2025. Accessed January 29, 2025.
3. Meglio, M. AXS-07 Meets Primary End Points, Halts Migraine Pain Progression. NeurologyLive. April 8, 2020. https://www.neurologylive.com/view/axs07-meets-primary-end-points-halts-migraine-pain-progression. Accessed January 29, 2025.