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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)
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)
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)
Ability to quickly return to normal activities reported by 51.0% of patients after SYMBRAVO versus 11.5% after oral CGRPs (p<0.001)
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:
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).
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).
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).
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
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
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.
For more information, visit www.symbravo.com.
What is SYMBRAVO (sim-BRAH-voh)? SYMBRAVO is a combination of meloxicam (an NSAID) and rizatriptan (a triptan). SYMBRAVO is an oral prescription medicine used to treat acute migraine headaches with or without aura in adults.
SYMBRAVO is not used to prevent or decrease the number of migraine headaches you have or for treatment of hemiplegic or basilar migraines. SYMBRAVO is not indicated as a treatment for cluster headaches or for use in children.
WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT SYMBRAVO?
SYMBRAVO may increase the risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase with increasing doses, and longer use, of NSAIDs.
Do not take SYMBRAVO right before or after a heart surgery called a “coronary artery bypass graft” (CABG).
Avoid taking SYMBRAVO after a recent heart attack unless your healthcare provider (HCP) tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.
Stop taking SYMBRAVO and get emergency help right away if you have any of the following symptoms which can be indicative of a heart attack or stroke:
discomfort in your chest that lasts for more than a few minutes, or that goes away and comes back
severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
pain or discomfort in your arms, back, neck, jaw, or stomach
shortness of breath with or without chest discomfort
breaking out in a cold sweat
weakness in one part or one side of your body
People with risk factors for heart disease should not take SYMBRAVO unless a heart exam is done and shows no problem. You have higher risk for heart disease if you:
have high blood pressure
have high cholesterol
have diabetes or a family history of diabetes
SYMBRAVO can increase the risk of potentially life-threatening bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach, and intestines that can occur anytime during use and without warning symptoms.
SYMBRAVO may cause serious allergic or skin reactions which can be life-threatening. Stop taking SYMBRAVO and get emergency help right away if you develop:
sudden wheezing or problems breathing or swallowing
rash or reddening of your skin with blisters or peeling
blisters or bleeding of your lips, eye lids, mouth, nose, or genitals
swelling of your lips, tongue, throat or body
SYMBRAVO already contains an NSAID (meloxicam). Do not use SYMBRAVO with other medicines to lessen pain or fever or with other medicines for colds or sleeping problems without talking to your HCP first, because they may contain an NSAID also.
Do not take SYMBRAVO if you:
have or had heart problems or right before or after heart bypass surgery
have or had a stroke or transient ischemic attack (TIA)
have or had blood vessel problems of your legs and arms, stomach (ischemic bowel disease), or kidneys
have or had hemiplegic or basilar migraines
have uncontrolled high blood pressure
take propranolol containing medicines
have taken other triptan or ergot-containing medicines within the last 24 hours
take an antidepressant medicine called monoamine oxidase inhibitor (MAOI) or have taken a MAOI within the last 2 weeks
are allergic to meloxicam, rizatriptan, NSAIDs, or any of the ingredients in SYMBRAVO
have had an asthma attack, hives, or other allergic reaction after taking aspirin or any other NSAIDs
have moderate to severe kidney problems and are at risk of kidney failure or if you are on dialysis
SYMBRAVO may cause serious side effects. These serious side effects include:
heartbeats that are too fast or too slow (arrhythmias)
new or worse high blood pressure
life-threatening skin reactions
liver or kidney problems including organ failure
low red blood cell count (anemia)
asthma attacks in people who have asthma
Medication Overuse Headaches: Some people who use too many SYMBRAVO tablets may have worse headaches. If your headaches get worse, your HCP may decide to stop your treatment with SYMBRAVO.
Stop taking SYMBRAVO and get emergency help right away if you have any of the following:
Stomach and intestinal problems. Symptoms of gastrointestinal and colonic ischemic events may include sudden or severe stomach pains even after meals; sudden weight loss; severe nausea, vomiting, constipation, diarrhea; and bloody diarrhea.
Circulation problems to legs and feet. Symptoms of peripheral vascular ischemia may include cramping and pain in your legs and hips; heaviness or tightness in leg muscles; burning, aching, numbness, tingling, or weakness in your legs, feet, or toes; cold feelings or color changes in one or both legs or feet.
Serotonin syndrome. Can happen when taking SYMBRAVO with antidepressant medicines called SSRIs or SNRIs. Stop taking SYMBRAVO and call your doctor right away if you have any of the following symptoms: mental status changes including agitation, hallucinations, or coma
changes in your blood pressure
increased body temperature
Stop taking SYMBRAVO and call your healthcare provider right away if you have any of the following symptoms:
more tired or weaker than usual
blood in your bowel movement or it is black and sticky like tar
itching, skin rash, or blisters with fever
your skin or eyes look yellow
indigestion or stomach pain
swelling of the arms, legs, hands, or feet
tenderness in your right upper side
The most common side effects of SYMBRAVO include dizziness and tiredness.
These are not all the possible side effects of SYMBRAVO. Tell your doctor if you have any side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1–800-FDA-1088.
Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
It is important to tell your HCP if you are taking: Propranolol containing medicines such as Inderal® LA or Innopran® XL
Aspirin or other anti-coagulants (blood thinners)
Medicines to help your mood including SSRIs and SNRIs
If you are unsure if you take any of these medicines, ask your HCP. They can tell you if it is safe to take SYMBRAVO with your other medicines.
Tell your HCP if you are pregnant or plan to become pregnant. SYMBRAVO is not recommended during pregnancy. Taking NSAIDs, including SYMBRAVO, at about 20 weeks of pregnancy or later may harm your unborn baby. NSAIDs, including SYMBRAVO, should not be taken after about 30 weeks of pregnancy.
Tell your HCP if you are breastfeeding or plan to breastfeed.
Tell your HCP about all your medical conditions, including if you:
have or have had heart problems, high blood pressure, chest pain, or shortness of breath
have any risk factors for heart or blood vessel problems
have kidney or liver problems
Review the list below with your HCP. SYMBRAVO may not be right for you if:
take daily preventative aspirin
you are pregnant or plan to become pregnant
you are breastfeeding or plan to breastfeed