Symbravo for Migraine Demonstrates Efficacy Superior to Prior CGRP Inhibitor Treatment in Phase 3 Trial

Symbravo (MoSEIC meloxicam and rizatriptan), the recently FDA-approved oral multimodal treatment for moderate-to-severe migraine in adults, met the primary endpoint in the EMERGE phase 3 clinical trial, demonstrating statistically significantly greater improvement in migraine treatment response compared to prior oral calcitonin gene-related peptide (CGRP) inhibitor therapy (P<.001), according to a news release from developer Axsome Therapeutics. Response was assessed by the Migraine Treatment Optimization Questionnaire (mTOQ-4) total score (5.2 vs 2.8, respectively).

Richard B Lipton, MD

Symbravo provided rapid and substantial pain relief, with nearly half (47.9%) of study participants achieving 2-hour pain freedom at least half the time vs just 1.0% reaching the endpoint with prior oral CGRP inhibitors(P<.001). Sustained pain relief for at least 24 hours after a single dose of Symbravo was reported by 47.9% vs 16.7% (P<.001), and 51.0% of participants were able to quickly return to normal activities vs 11.5% (P<.001). Moreover, 63.5% of Symbravo-treated participants reported being “comfortable enough with their medication” that they were able to plan daily activities half or more of the time after treatment compared with 26.0% after treatment with oral CGRP inhibitors.

Quality of life improvements as assessed with the Migraine-Specific Quality of Life Questionnaire (MSQ), also were statistically significant (P<.001), according to Axsome.

“The results of the EMERGE study demonstrate significant improvements in migraine treatment response with Symbravo for patients previously experiencing inadequate response to oral CGRPs based on the mTOQ-4 [Migraine Treatment Optimization Questionnaire],” Richard B. Lipton, MD, professor of neurology and director of the Montefiore Headache Center, Albert Einstein College of Medicine, said in the statement. “Migraine is a disabling neurological condition, and the multiple mechanisms of action of Symbravo may be relevant to the complex and heterogeneous nature of this serious condition. These data from the EMERGE study are compelling and provide further evidence for the utility of Symbravo across a variety of migraine settings.”

EMERGE was a phase 3 open-label trial enrolling 96 adults with migraine who had inadequate response to previous therapy for migraine with oral CGRP inhibitors after at least 1 month of use prior to enrollment and having treated at least 4 migraines with the medications. Participants treated their next 4 attacks with Symbravo, and results were compared to their previous oral CGRP inhibitor treatment. A total of 365 migraine attacks were treated with Symbravo.

Additional findings across multiple efficacy measures for Symbravo compared with previous CGRP inhibitor use included:

• Half of EMERGE participants receiving Symbravo achieved relief within 2 hours in at least half of their treated attacks
• Pain relief was sustained through 24 and 48 hours in 78% and 75% of participants, respectively. Pain freedom and freedom from the most bothersome symptom at 2 hours were achieved by 22.5% and 26.6% of participants, respectively
• Improvement in overall migraine condition was reported by 26.0% of participants within 30 minutes and by 69.2% at 2 hours post-dose

Symbravo was well tolerated, with an adverse event profile consistent with prior studies. The most commonly reported adverse events (≥2%) included fatigue (3.1%), nausea (3.1%), vomiting (2.1%), muscle tightness (2.1%), and dizziness (2.1%).

“We’re pleased to share the results of the Phase 3 EMERGE trial, which further underscore the robust efficacy of Symbravo and its potential to effectively treat migraine attacks across a range of patient populations with varying pain intensities and prior responses to acute treatments. We look forward to launching Symbravo in the U.S. in the coming months and offering a new treatment option that could make a meaningful difference for patients suffering from this disabling condition,” Herriot Tabuteau, MD, chief executive officer of Axsome Therapeutics, stated.

Inadequate response to prior CGRP inhibitor therapy was defined by an mTOQ-4 score ≤7, including a score of 1 (“less than half the time”) or 0 (“rarely” or “never”) on achieving 2-hour pain freedom. Enrolled patients switched from oral CGRP inhibitors to Symbravo for 4 migraine attacks over up to eight weeks.

The mTOQ-4 questionnaire evaluates acute migraine treatment efficacy, assessing 2-hour pain freedom, sustained pain freedom, ability to return to activities, and comfort in planning daily activities. Scores range from 0 to 8, with higher scores indicating greater treatment optimization.

Migraine is a debilitating neurological condition affecting more than 39 million Americans. It is the leading cause of disability among neurologic disorders in the US, according to the American Migraine Foundation.23 Findings from numerous surveys of adults with migraine underscore the unmet need for faster, more consistent treatments with less symptoms recurrence. More than 70% of patients report inadequate response to their acute migraine treatment.

Symbravo is an oral, single-dose treatment approved for acute migraine with or without aura in adults. It combines meloxicam, a COX-2 preferential NSAID enabled by MoSEIC technology for rapid absorption, and rizatriptan, a 5-HT1B/1D agonist. Symbravo is designed to provide fast, enhanced, and consistent migraine relief with reduced symptom recurrence.