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SYMBRAVO demonstrated statistically significantly greater migraine treatment response compared to prior treatment with an oral CGRP inhibitor (p<0.001, mTOQ-4 total score, primary endpoint)
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2-hour pain freedom for most attacks reported at least half the time by 47.9% of patients after SYMBRAVO versus 1.0% after oral CGRPs (p<0.001)
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24-hour or greater sustained pain relief after a single dose reported by 47.9% of patients after SYMBRAVO versus 16.7% after oral CGRPs (p<0.001)
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Ability to quickly return to normal activities reported by 51.0% of patients after SYMBRAVO versus 11.5% after oral CGRPs (p<0.001)
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SYMBRAVO improved quality of life compared to after oral CGRPs (p<0.001, MSQ)
NEW YORK, Feb. 24, 2025 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced that the EMERGE Phase 3 trial of SYMBRAVO® (MoSEIC™ meloxicam and rizatriptan) in patients experiencing inadequate response to oral CGRP inhibitors met its primary endpoint, with SYMBRAVO demonstrating statistically significantly greater migraine treatment response compared to oral CGRP inhibitors, as measured by the Migraine Treatment Optimization Questionnaire (mTOQ-4). SYMBRAVO is a novel multi-mechanistic approach to treating migraine that targets multiple pathways underlying a migraine attack. In the trial, SYMBRAVO rapidly and substantially improved migraine pain and most bothersome symptoms.
EMERGE was an open-label trial that enrolled migraine patients who were undergoing treatment with an oral CGRP inhibitor for at least one month and experiencing an inadequate response to the oral CGRP inhibitor, with treatment response assessed using the mTOQ-4. Enrolled patients were switched to treatment with SYMBRAVO for their next four attacks. Treatment responses after the oral CGRP inhibitor treatment period and after the SYMBRAVO treatment period were compared. A total of 96 patients were enrolled and 365 migraine attacks were treated with SYMBRAVO in the trial.
EMERGE met the primary endpoint by demonstrating statistically significantly greater migraine treatment response with SYMBRAVO compared to treatment response with prior oral CGRP inhibitors, as assessed by the mTOQ-4 total score (5.2 versus 2.8, p<0.001). Statistically significantly greater proportions of patients achieved clinical response on the 2-hour pain freedom, sustained pain freedom, ability to return to normal activities, and ability to plan daily activities mTOQ-4 items with SYMBRAVO compared to oral CGRP inhibitors:
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Pain freedom within 2 hours for most attacks was reported half the time or more by 47.9% of patients after treatment with SYMBRAVO, compared to 1.0% of patients after treatment with oral CGRPs (p<0.001).
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Sustained relief of migraine pain for at least 24 hours following a single dose of medication was reported half the time or more by 47.9% of patients after treatment with SYMBRAVO, compared to 16.7% of patients after treatment with oral CGRPs (p<0.001).
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The ability to quickly return to normal activities after taking their medication was reported half the time or more by 51.0% of patients after treatment with SYMBRAVO, compared to 11.5% of patients after treatment with oral CGRPs (p<0.001).
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The proportion of patients who reported being comfortable enough with their medication to be able to plan daily activities half the time or more was 63.5% after treatment with SYMBRAVO, compared to 26.0% after treatment with oral CGRPs (p<0.001).
Further, SYMBRAVO treatment resulted in a statistically significant improvement in overall quality of life and daily functioning, as assessed by all three domains of the Migraine-Specific Quality of Life Questionnaire (MSQ), compared to after treatment with oral CGRP inhibitors (p=0.003 to <0.001).
Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center, Albert Einstein College of Medicine, commented, “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 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.”
In this population of patients with a prior inadequate response to an oral CGRP inhibitor, SYMBRAVO rapidly and substantially relieved migraine pain within 2 hours, with benefits sustained through 24 and 48 hours after a single dose. Across all treated attacks, pain relief 2 hours after dosing with SYMBRAVO was achieved by 50.0% of patients, with some patients experiencing pain relief as early as 30 minutes after dosing. The pain relief achieved 2 hours after dosing was sustained through 24 and 48 hours by 78% and 75% of patients respectively. Pain freedom and freedom from the most bothersome symptom 2 hours after dosing with SYMBRAVO was achieved by 22.5% and 26.6% of patients, respectively.
Overall improvement of migraine, measured using the Patient Global Impression of Change (PGI-C), was experienced early and in a substantial proportion of patients after treatment with SYMBRAVO. Overall improvement of their migraine was reported by 26.0% of patients 30 minutes post dose, and by 69.2% of patients 2 hours post dose.
SYMBRAVO was well tolerated with a safety profile that was consistent with what has been previously observed in prior studies. The most commonly reported adverse events (≥2%) were fatigue (3.1%), nausea (3.1%), vomiting (2.1%), muscle tightness (2.1%), and dizziness (2.1%).
Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, said, “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.”
About the EMERGE Trial
EMERGE (Evaluating Outcomes of AXS-07 after Acute Gepant Failures) was a Phase 3, open-label, multicenter trial to evaluate the efficacy and safety of SYMBRAVO in the acute treatment of migraine in patients experiencing inadequate response to an oral calcitonin gene-related peptide (CGRP) inhibitor. Eligible patients must have been using an oral CGRP inhibitor for the acute treatment of migraine for at least 1 month prior to enrollment (having treated at least 4 migraines with an oral CGRP inhibitor) and have had an inadequate response to the oral CGRP inhibitor. An inadequate response was defined as a score of ≤7 on the Migraine Treatment Optimization Questionnaire (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). Enrolled patients were switched from their oral CGRP inhibitor to SYMBRAVO and treated the next 4 migraine attacks with SYMBRAVO over a period of up to 8 weeks. A total of 96 patients were enrolled in the trial. The primary efficacy endpoint to assess treatment response with SYMBRAVO versus oral CGRP inhibitors was the change in the mTOQ-4 total score from the oral CGRP inhibitor treatment period to the SYMBRAVO treatment period.
About the Migraine Treatment Optimization Questionnaire (mTOQ-4)
The mTOQ-4 is a validated questionnaire that assesses the adequacy of migraine treatment efficacy based on four aspects of response to acute treatment: 2-hour pain freedom; sustained pain freedom; ability to quickly return to daily activities; and comfort planning daily activities. Each of the 4 items is scored, using frequency-based options, as never [0], rarely [0], less than half the time [1], and half of the time or more [2]. Total scores range from 0 to 8 with higher total scores corresponding to greater treatment optimization. A total score of 8 corresponds to maximum treatment efficacy, with total scores of 4-7 corresponding to moderate, 1-3 to poor, and 0 to very poor treatment optimization.1
About Migraine
Migraine is a serious neurological condition characterized by recurrent attacks of pulsating, often severe and disabling head pain associated with nausea, sensitivity to light, and sensitivity to sound.2 It is estimated that over 39 million Americans suffer from migraine, and it is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation.3-5 Extensive surveys of migraine sufferers underscore the unmet need for therapies that work faster, more consistently, and result in less symptom recurrence.6,7 Over 70% of patients report experiencing an inadequate response to their oral, acute migraine treatment.8
About SYMBRAVO
SYMBRAVO is a novel, oral, single-dose medicine approved for the acute treatment of migraine with or without aura in adults. SYMBRAVO consists of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which enables the rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug (NSAID) and rizatriptan is a 5-HT1B/1D agonist. SYMBRAVO is designed to provide rapid, enhanced, and consistent migraine pain relief, and reduced symptom recurrence. The exact mechanism of action of SYMBRAVO in the treatment of acute migraine is unknown.
About Axsome Therapeutics
Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder, excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, and migraine, and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish.
References
1.Lipton RB, Fanning KM, et al. Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine. Neurology. 2015;84(7):688-695.
2.Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38:1-211.
3.Ashina M, Katsarava Z et al. Migraine: epidemiology and systems of care. Lancet. 2021 Apr 17;397(10283):1485-1495.
4.American Migraine Foundation. 2023.
5.Steiner TJ et al. Migraine remains the second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020 Dec 2;21(1):137.
6.Smelt AF, Louter MA et al. What do patients consider to be the most important outcomes for effectiveness studies on migraine treatment? Results of a Delphi study. PLoS One. 2014 Jun 16;9(6):e98933.
7.Lipton RB, Stewart WF. Acute migraine therapy: do doctors understand what patients with migraine want from therapy? Headache. 1999;39(suppl 2):S20-S26.
8.Lipton RB, Munjal S et al. Unmet Acute Treatment Needs From the 2017 Migraine in America Symptoms and Treatment Study. Headache. 2019 Sep;59(8):1310-1323.