The U.S. Food and Drug Administration (FDA) has approved Symbravo (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults. Developed by Axsome Therapeutics, Symbravo offers a novel, multi-mechanistic approach targeting multiple pathways underlying migraine attacks. The company expects the drug to be available in the U.S. in approximately four months. This approval marks a significant advancement in migraine treatment, providing a new option for the over 39 million Americans who suffer from this debilitating condition.
Clinical Efficacy
The FDA's decision was based on data from three Phase 3 trials: MOMENTUM, INTERCEPT, and MOVEMENT. These trials collectively treated over 21,000 migraine attacks with Symbravo.
In the MOMENTUM trial, Symbravo demonstrated a statistically significant greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom (photophobia, phonophobia, nausea) two hours after dosing compared to placebo (p<0.001). Benefits of pain freedom were sustained through 24 and 48 hours for many patients. 77% of patients treated with Symbravo did not require rescue medication within 24 hours post-dose.
The INTERCEPT trial, which treated migraine when the initial pain was mild, showed similar results. Symbravo demonstrated a statistically significantly greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom two hours after dosing compared to placebo (p<0.001). 85% of patients treated with Symbravo did not require rescue medication within 24 hours post-dose.
The MOVEMENT trial demonstrated the long-term safety of Symbravo, with the most common adverse events being somnolence and dizziness.
Expert Opinions
Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center, Albert Einstein College of Medicine, commented, “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. Results of multiple clinical trials demonstrate that Symbravo 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 Symbravo is a long awaited and much welcomed advancement for clinicians and our patients, providing a new, meaningful treatment option.”
Stewart Tepper, MD, Clinical Professor of Neurology at the Geisel School of Medicine at Dartmouth, added, “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. 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.”
Mechanism of Action and Technology
Symbravo combines meloxicam, a COX-2 preferential non-steroidal anti-inflammatory drug (NSAID), and rizatriptan, a 5-HT1B/1D agonist (triptan). Axsome’s MoSEIC™ (Molecular Solubility Enhanced Inclusion Complex) technology enables the rapid absorption of meloxicam while maintaining a long plasma half-life.
EMERGE Trial Results
In a Phase 3 EMERGE trial, SYMBRAVO significantly improved migraine treatment response compared to oral CGRP inhibitors (p<0.001), as measured by the Migraine Treatment Optimization Questionnaire (mTOQ-4). 47.9% of patients reported pain freedom within 2 hours for most attacks after SYMBRAVO, compared to 1.0% after oral CGRPs (p<0.001). Sustained pain relief for at least 24 hours was reported by 47.9% of patients after SYMBRAVO versus 16.7% after oral CGRPs (p<0.001).
Safety and Availability
The most common adverse reactions (≥1% and greater than placebo) in the controlled studies were somnolence and dizziness. Axsome expects Symbravo to be commercially available in the U.S. in approximately four months.
