Migraine Medication Symbravo Demonstrates Therapeutic Efficacy in Patients Unresponsive to CGRPs

Richard B. Lipton, MD

In the phase 3 EMERGE trial (NCT05550207), newly announced data revealed that AXS-07 (Symbravo; Axsome Therapeutics), a recently approved medication for migraine, met its primary end point in migraine treatment response relative to placebo in a cohort of patients who’ve previously failed oral calcitonin gene-related peptide (CGRP) inhibitors.¹

AXS-07, which consists of meloxicam and rizatriptan, is thought to act by inhibiting CGRP release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization. In EMERGE (n = 96), treatment with AXS-07 resulted in greater migraine treatment response relative to prior oral CGRP inhibitors, as assessed by changes in Migraine Treatment Optimization Questionnaire (mTOQ-4) total score (5.2 vs 2.8; P <.001) over the 8-week treatment period.

In the study, enrolled patients were switched from their oral CGRP inhibitor to AXS-07 and treated and had their next 4 migraine attacks treated with AXS-07 over a period of up to 8 weeks. Results showed that 47.9% of treated patients on AXS-07 demonstrated pain freedom within 2 hours for most attacks, compared with 1.0% of those after treatment with oral CGRPs (P <.001).

"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, said in a statement.¹ "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."

Treatment with AXS-07 demonstrated superior outcomes compared to oral CGRP inhibitors, with 47.9% of patients reporting sustained migraine pain relief for at least 24 hours following a single dose, compared to 16.7% with oral CGRPs (P <0.001). Additionally, 51.0% of patients reported the ability to quickly resume normal activities after AXS-07 treatment versus 11.5% with oral CGRPs (P <0.001), and 63.5% felt comfortable planning daily activities, compared to 26.0% with oral CGRPs (P <0.001). AXS-07 also significantly improved overall quality of life and daily functioning across all domains of the Migraine-Specific Quality of Life Questionnaire (MSQ; P =0.003 to <0.001).

EMERGE, a unique, open-label trial, had its first participant dosed in September 2022. The trial, which features patients with or without aura, excludes those who are pregnant, breastfeeding, or planning to become pregnant, as well as those who had received any investigational drug or device within 30 days of screening. Investigators defined an inadequate response to CGRP-targeting treatments as a score of 7 or less on the mTOQ-4, including a score of 1 (less than half the time) or 0 (rarely or never) on question 2 (achievement of pain freedom 2 hours after taking migraine medication).

On Patient Global Impression of Change (PGI-C), 26.0% of AXS-07-treated patients reported improvement of their migraine 30 minutes post dose and 69.2% saw enhancements 2 hours post dose. The multi-mechanistic agent also demonstrated a safety profile that was similar to previous observations, as the most commonly reported adverse events were fatigue (3.1%), nausea (3.1%), vomiting (2.1%), muscle tightness (2.1%), and dizziness (2.1%).

Herriot Tabuteau, MD

"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," Herriot Tabuteau, MD, chief executive officer at Axsome, said in a statement.¹ "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."

AXS-07 gained FDA approval earlier this month based on data from 2 phase 3 randomized controlled trials—the MOMENTUM trial (NCT03896009) and the INTERCEPT trial (NCT04163185). In those studies, treatment with the oral medication led to a statistically significant elimination of migraine pain relative to placebo and active controls. In MOMENTUM, AXS-07 met its coprimary end points with statistical significance, first showing a greater percentage of patients achieving pain freedom (19.9%) compared with placebo (6.7%; P <.001) 2 hours after dosing. Second, the absence of the most bothersome symptom (36.9%) compared with placebo (24.4%) was significant (P = .002).^2,3

Following the approval, Lipton sat down with NeurologyLive® to discuss the safety and efficacy considerations of AXS-07 in the context of treating patients with migraine. In the clip below, he addressed the specific patient populations that may derive the most value from this approach, emphasizing the importance of selecting therapies based on individual treatment needs. Additionally, he underscored the critical role of timing in migraine treatment, explaining that early intervention can significantly improve treatment outcomes and overall patient response.

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://www.globenewswire.com/news-release/2025/02/24/3031008/33090/en/Axsome-Therapeutics-Announces-SYMBRAVO-meloxicam-and-rizatriptan-Achieves-Primary-Endpoint-in-the-EMERGE-Phase-3-Trial-in-Migraine-Patients-Experiencing-Inadequate-Response-to-Oral.html
2. Axsome Therapeutics Announces FDA Approval of SYMBRAVO® (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults. News Release. Axsome Therapeutics. Published January 30, 2025. Accessed February 24, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam
3. Axsome Therapeutics Announces AXS-07 Achieves Co-Primary and Key Secondary Endpoints in MOMENTUM Phase 3 Migraine Trial in Patients with History of Inadequate Response. News release. Axsome Therapeutics. December 30, 2019. Accessed February 24, 2025. https://www.biospace.com/article/releases/axsome-therapeutics-announces-axs-07-