A single oral dose of Symbravo provided rapid migraine pain freedom and return to normal functioning within 2 hours, and sustained efficacy through 24 and 48 hours.
The FDA has approved Symbravo (meloxicam and rizatriptan) for the acute treatment of migraine, with or without aura, according to a news release January 30, 2025 from developer Axsome Therapeutics.1 The company expects Symbravo to be commercially available in the US in approximately 4 months.
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 In clinical trials, the NSAID/triptan combination resulted in efficacy sustained through 24 and 48 hours in some patients after a single dose, according to Axsome. Across the phase 3 development program, the novel medication’s efficacy was shown over a broad range of migraine scenarios including at the earliest onset of pain, in adults with moderate to severe pain, and in those with a history of variable response to prior acute treatments.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
The FDA approval is based on findings from 3 pivotal phase 3 clinical trials: MOMENTUM,3 which enrolled participants with migraine of moderate to severe intensity who had poor response to previous therapies. Symbravo met the coprimary regulatory endpoints with statistical significance, with a greater percentage of patients achieving pain freedom at 2 hours post-dose (19.9%) compared with placebo (6.7%; P <.001) and freedom from the most bothersome symptom (36.9%) compared with placebo (24.4%; (P = .002) 2 hours after dosing. When compared directly with rizatriptan, Symbravo was statistically significantly superior on sustained pain freedom from 2 to 24 hours. In this trial, more than three-quarters of Symbravo-treated participants did not require rescue medication within 24 hours after taking the medication.3
INTERCEPT targeted early intervention with Symbravo, with participants taking a single dose when migraine pain was mild.4 All told, the coprimary end points echoed results seen in MOMENTUM, with a statistically significantly greater percentage of participants 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). Symbravo was also effective in preventing progression of migraine pain beyond mild intensity and significantly reducing the use of rescue medication, with 85% of Sybmravo-treated participants achieving freedom of pain progression compared with 47.4% of those treated with placebo between 2 and 24 hours post dose.4
A pooled analysis of the MOMENTUM and INTERCEPT trials presented at the 2024 American Academy of Neurology Annual Meeting5 confirmed the findings of both trials with Symbravo associated with 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.5
Symbravo returned high and consistent efficacy across sequential migraine attacks and was well-tolerated over the course of 1 year in the MOVEMENT long-term open label safety trial, the company reported.1
It is estimated that more than 39 million Americans suffer from migraine, and it is the leading cause of disability among neurologic disorders in the US according to the American Migraine Foundation.6
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