Symbravo Outperforms Oral CGRP Inhibitors in Phase III Trial, With Faster, Sustained Migraine Relief

Credit: Damir Khabirov | stock.adobe.com

Results from the Phase III EMERGE trial (NCT05550207) show that treatment with Symbravo (MoSEIC meloxicam and rizatriptan; Axsome Therapeutics) produced a significant improvement compared to oral calcitonin gene-related peptide (CGRP) inhibitors in migraine treatment response, pain relief, and quality of life in patients who previously had an inadequate response to CGRPs.^1,2 Trial investigators stated that these findings indicate Symbravo can provide more rapid and sustained pain relief for this patient population with an unmet need for migraine treatment options.

“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,” Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center, Albert Einstein College of Medicine, said in a press release. “Migraine is a disabling neurological condition, and the multiple mechanisms of action of Symbravo may be relevant to the complex and heterogenous 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.”¹

Symbravo combines rizatriptan with Axsome’s MoSEIC rapid absorption technology to improve the bioavailability of meloxicam. The FDA approved Symbravo last month for the acute treatment of adults with migraine with or without aura.

The FDA based the regulatory action on results from the Phase III MOMENTUM, INTERCEPT, and MOVEMENT trials. Combined data from these trials show Symbravo produced statistically significant pain freedom and symptom relief at two hours post-dose, with sustained benefits compared to placebo and rizatriptan monotherapy.³

Trial Design

The open-label, multicenter EMERGE trial analyzed the efficacy and safety of Symbravo in the acute treatment of migraine in patients who did not achieve an inadequate response to an oral CGRP inhibitor. Eligibility requirements included prior use of an oral CGRP inhibitor for at least four acute migraine attacks at least one month before enrolling in the trial with an inadequate response to the oral CGRP inhibitor.

Investigators enrolled 96 patients in the trial, who were switched from an oral CGRP inhibitor to Symbravo, which was used to treat their next four migraine attacks for a period lasting up to eight weeks. The trial’s primary efficacy endpoint was an analysis of change in mTOQ-4 total score with Symbravo compared to CGRP inhibitors.

The results showed a statistically significantly improvement for the primary endpoint of migraine treatment response, with patients administered Symbravo having an mTOQ-4 total score of 5.2 compared to 2.8 (p<0.001) with oral CGRP inhibitors. Further, 47.9% of patients administered Symbravo reported two-hour pain freedom compared to 1.0% of patients administered oral CGRPs.

A total of 47.9% of patients of patients administered Symbravo experienced sustained migraine pain relief for at least 24 hours compared with 16.7% of patients administered oral CGRPs (p<0.001). Additionally, 51.0% of patients treated with Symbravo were able to resume daily activities compared to 11.5% of patients with oral CGRPs.

“We’re pleased to share the results of the Phase III 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,” Herriot Tabuteau, MD, chief executive officer of Axsome Therapeutics, in the release. “We look forward to launching Symbravo in the US in the coming months and offering a new treatment option that could make a meaningful difference for patients suffering from this disabling condition.”¹

References

1. Axsome Therapeutics Announces SYMBRAVO® (meloxicam and rizatriptan) Achieves Primary Endpoint in the EMERGE Phase 3 Trial in Migraine Patients Experiencing Inadequate Response to Oral CGRP Inhibitors. News release. Axsome Therapeutics. February 24, 2025. Accessed February 24, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-symbravor-meloxicam-and

2. Open-Label Study of AXS-07 for the Acute Treatment of Migraine in Adults With a Prior Inadequate Response to an Oral CGRP Inhibitor (EMERGE). ClinicalTrials.gov. Updated January 20, 2025. Accessed February 24, 2025. https://clinicaltrials.gov/study/NCT05550207

3. Axsome Therapeutics Announces FDA Approval of SYMBRAVO® (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults. Axsome Therapeutics. January 30, 2025. Accessed February 24, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam