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The pediatric neurologist at Children’s Hospital of Philadelphia provided background on a notable track session at the upcoming MDA Clinical & Scientific Conference covering updates in gene therapy for neuromuscular conditions. [WATCH TIME: 4 minutes]

Navigating the Future of Gene Therapy in Neuromuscular Disorders: John Brandsema, MD

Articles

A pair of lead neurologists at Baptist Health South Florida provided commentary on some of the promising developments expected to emerge in neurology over the coming months.

Exciting Innovations in Neurology to Come in 2025: Insights From Baptist Health

The assistant professor in the neurology department at the University of Utah in Salt Lake City discussed the importance of addressing broader quality-of-life measures in patients with NMOSD beyond just preventing relapses. [WATCH TIME: 3 minutes]

Managing NMOSD Disease Progression Through Healthy Habits and Holistic Care: Tammy Smith, MD, PhD

Marketed as Wakix, the treatment is currently approved in the United States for excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy and for EDS in pediatric patients aged 6 and older.

FDA Refuses to File Harmony’s Supplemental NDA of Pitolisant in Idiopathic Hypersomnia

Attending Physician, Neuromuscular/General Neurology & Electromyography; Neuromuscular Education Director and Neuromuscular Section Head, Children’s Hospital of Philadelphia

Marco Meglio, Assistant Managing Editor for 

, has been with the team since October 2019. Follow him on Twitter 

Associate professor of neurology, Columbia University; Medical consultant and care center director, Muscular Dystrophy Association

The associate professor of neurology at Columbia University gave clinical insight on what neurologists and other neuromuscular specialists can expect from the ALS/frontotemporal dementia track at this year’s MDA Clinical & Scientific Conference. [WATCH TIME: 3 minutes]

Advancing Therapeutic Knowledge of Genetic Influence in ALS: Matthew B. Harms, MD

NeurologyLive is your direct connection to the latest neurology news and interviews with expert neurologists in multimedia formats.

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Pediatric epilepsy specialist at University of California, San Francisco.

Pediatric epilepsy specialists Adam Numis, MD, and Laura Kirkpatrick, MD, highlighted efforts to standardize data collection for pediatric epilepsy health equity and improve neonatal epilepsy outcomes.

Pediatric AES Insights: Addressing Health Disparities and Advancing Neonatal Epilepsy Care

At AES 2024, a duo of pediatric epilepsy specialists discussed how implementation science, validated blood biomarkers, and cross-disciplinary collaboration are advancing epilepsy care and closing research gaps. [WATCH TIME: 3 minutes]

Advancing Epilepsy Research Through Implementation Science and Biomarkers: Adam Numis, MD; Laura Kirkpatrick, MD

At AES 2024, a duo of pediatric epilepsy specialists highlighted a Pediatric Epilepsy Research Consortium review on the need for standardized socio-demographic data and better follow-up for at-risk infants. [WATCH TIME: 5 minutes]

Addressing Disparities and Improving Care Through Pediatric Epilepsy Research: Adam Numis, MD; Laura Kirkpatrick, MD

 identified specific cerebrospinal fluid (CSF) lipids that distinguished multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD) and other neurological diseases with high accuracy, offering potential new biomarkers for diagnosis and disease monitoring. The research also reported correlations between CSF lipid levels and measures of disease activity, including Expanded Disability Status Scale (EDSS) scores and inflammatory cytokines.

In the study, researchers screened 353 lipid species in pooled CSF samples, quantifying 161 lipids across patients diagnosed with MS and NMOSD by clinical criteria as well as other inflammatory neurological diseases (OIND), and non-inflammatory neurological diseases (NIND). Significant differences emerged in the results, particularly in NMOSD, where 29 lipids—including sphingolipids and polyunsaturated lysophosphatidylcholines (LPCs)—were significantly elevated compared with MS.

"My understanding, from speaking to neuroimmunology specialists, is that diagnosis of AQP4 antibody-positive NMOSD is relatively clear-cut. The benefit of an alternative diagnosis will be distinguishing NMOSD from MS for AQP4 antibody-negative NMOSD, which I believe is somewhere in the range of 20-40% of NMOSD cases," senior author Anthony Don, PhD, a professor of medical biochemistry at the University of Sydney School of Medical Sciences, told 

in a recent interview. "We achieved very good differentiation of NMOSD from MS based on levels of just 3 lipids, and these lipids are easy to quantify with mass spectrometry systems that are used in clinical diagnostic labs. So an assay based on CSF or serum lipids would be quite easy to adapt for clinical practice, and low cost."

Further analysis showed that NMOSD cases exhibited higher levels of specific lipid classes, such as dihexosylceramides (Hex2Cer) and sphingomyelins (SM), compared with MS and NIND. A subset of OIND cases, including conditions like neurosarcoidosis and CNS lymphoma, also had elevated lipid levels similar with NMOSD. A machine-learning approach using partial least squares discriminant analysis and random forest analysis revealed that a combination of 3 lipids—GM3(d42:2), Hex2Cer(d18:1/22:0), and GM3(d38:1)—achieved 91% sensitivity and 91% specificity in differentiating NMOSD from MS. Notably, Hex2Cer(d18:1/22:0) alone distinguished NMOSD from MS with 73% sensitivity and 100% specificity at a threshold of 1.1 nmol/L CSF.

Dubai Study Highlights Disease Characteristics and Treatment Outcomes in NMOSD and MOGAD

Beyond diagnostic potential, the study examined how CSF lipids correlated with inflammatory cytokines and measures of disease activity. Several sphingolipids and LPC species were positively associated with inflammatory markers, including macrophage migration inhibitory factor (MIF), interleukin-6, and CXCL13, a chemokine involved in B-cell recruitment. Notably, 94 lipids were significantly correlated with MIF levels, with the strongest associations observed in SMs, Hex2Cers, and LPCs. Although MIF was elevated in NMOSD, it was also higher in patients with MS experiencing relapse compared with those in remission.

"Prior studies have not really looked at associations of lipid levels with inflammatory cytokines. We did this to determine if the increased levels of lipids in the CSF of [patients] with NMOSD reflect some kind of inflammatory signature and I was surprised by how strongly levels of many lipids in the CSF were correlated with the cytokine MIF. MIF is higher in [pateints] with NMOSD compared [with] MS or control [participants], so the correlation makes sense," Don explained. 

"Sphingolipid levels were higher in the CSF of [patients] with NMOSD but not MS (in fact they were higher in NMOSD compared [with] MS), so I’m not sure that CSF sphingolipids would be useful biomarkers for MS," Don added. "I think the finding of high levels of sphingolipids in the CSF of [patients] with NMOSD is clinically-relevant and should be explored as a biomarker of treatment response for that disease. Sphingolipids in the serum may be more poignant for MS and that will be discussed in a forthcoming paper."

In MS, gadolinium-enhancing (Gd+) lesions indicated active inflammation and blood-brain barrier disruption. In the study, 39 lipids, primarily phosphatidylcholine, triglycerides, and cholesterol esters (CEs), were significantly reduced in the CSF of patients with MS who had Gd+ lesions compared with those without. Notably, EDSS scores were inversely correlated with certain cholesterol esters, particularly CE(16:0), CE(22:5), and CE(22:6). Despite this correlation, the overall mean levels of these lipids did not significantly differ between disease groups.

"There is no obvious explanation for the inverse correlation between EDSS and CE(16:0), however we saw the association in 2 independent sample sets. Myelin is a vast reservoir of cholesterol, which cannot be broken down by the macrophages and microglia that degrade myelin in MS. Instead, they store the excess cholesterol that is released from the degraded myelin in the form of cholesterol esters," Don said. "Lower cholesterol ester levels in association with higher EDSS could reflect reduced cholesterol efflux from myelin plaques into the CSF as the disease progresses and plaques become chronic, or perhaps increased efflux across a leaky CSF-blood barrier. To determine if this correlation is relevant for monitoring treatment response, we would need to determine how CSF cholesterol ester levels vary over time and as a function of therapeutic response." 

Despite the study providing compelling set evidence that CSF lipids could serve as biomarkers for NMOSD and MS, authors acknowledged that several limitations exist. Researchers noted that the NMOSD sample size was relatively small, which prevented further stratification based on AQP4 antibody status. Additionally, the study did not include progressive MS cases, leaving questions about whether lipid differences extend beyond relapsing-remitting MS. Investigators also highlighted that the lack of healthy controls also meant that normal CSF lipid ranges could not be established.

All told, the current study underscored the potential of CSF lipids as biomarkers for differentiating NMOSD from MS and tracking disease activity. By identifying lipid profiles associated with inflammation and disability, these findings could pave the way for improved diagnostic and monitoring tools in neuroinflammatory diseases. Authors recommended that future research should validate these findings in larger cohorts and investigate whether lipid changes correlate with MRI measures of demyelination and therapeutic response.

"I think it is too early to talk about translation of CE(16:0) as a biomarker for MS. As mentioned [earlier], these lipids are not that challenging to measure with modern clinical mass spectrometers, but a plasma or serum biomarker would be better for MS and it is probably only a matter of time until we find a good one. I am not a clinical practitioner and they may have a different perspective," Don said.

REFERENCES
1. Shi L, Ghezzi L, Fenoglio C, et al. CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis. J Neurol Neurosurg Psychiatry. 2024;96(1):54-67. Published 2024 Dec 16. doi:10.1136/jnnp-2024-333774
2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2
3. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/WNL.0000000000001729

A study identified specific cerebrospinal fluid (CSF) lipids that differentiate multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD) and other neurological diseases, suggesting potential biomarkers for diagnosis and monitoring. Researchers screened 353 lipid species, finding significant differences, particularly in NMOSD. A machine-learning approach identified three lipids achieving high sensitivity and specificity in differentiating NMOSD from MS. CSF lipids correlated with inflammatory cytokines and disease activity measures. Despite promising results, limitations include small sample size and lack of healthy controls, necessitating further research for validation.

Cerebrospinal fluid lipid profiling revealed potential biomarkers for distinguishing NMOSD from MS and tracking disease activity, offering new insights into neuroinflammatory disease monitoring. 

Clinical

Cerebrospinal Fluid Lipids Shows Promise as Biomarkers for Differentiating NMOSD and MS

Nearly 4 and a half years since its original submission, the FDA has approved Supernus Pharmaceuticals’ investigational agent SPN-830 (Onapgo) as the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company also noted that it will make SPN-830 available in the second quarter of 2025 with a support team of experts, including a robust nurse education program, and access support at launch.

"People living with Parkinson's and their families are hungry for new treatment options, and the PMD Alliance community was thrilled to learn about SPN-830's approval. Every newly approved Parkinson's therapy is a win for our community," 

 in a recent interview. "The introduction of this therapy brings with it an increased need for education, and underscores the importance of clinician-patient communication. PMD Alliance produces resources and education to help patients understand their symptoms, for personal empowerment, but also to streamline clinic visits. Our annual healthcare provider conference, 

Advanced Therapeutics in Movement and Related Disorders (ATMRD)

, equips clinicians with the information to integrate new therapies into practice."

The therapy’s approval was based on data from the TOLEDO study (NCT02006121), a randomized, double-blind study in which treatment with the device was associated with a difference of –1.89 hours per day of OFF time for patients with PD in comparison with placebo. Published in the 

in 2018, the study randomly assigned 106 patients living with the disease to either 3-mg/hour to 8-mg/hour dose of apomorphine (n = 53) or placebo saline infusion (n = 53) during their wake hours for a 12-week period.

"Hope is strong after this approval, the third in less than a year. Combined with momentum from the 

 being signed into law, 2025 has the potential to be a banner year for people living with Parkinson's and the healthcare providers caring for them," Merriam said. 

In TOLEDO, the intervention group, with a mean final drug dose of 4.68 mg/hour, showed significant improvements, including a reduction in OFF time of –2.47 hours/day compared with –0.58 hours/day for placebo (

 = .0025), and an increase in ON time without troublesome dyskinesia of 2.77 hours/day versus 0.80 hours/day for placebo (

 = .0008). Additionally, 62% of the apomorphine group were responders compared with 29% in the placebo group (P = .0008).

"The approval of ONAPGO (SPN-830) is a significant milestone in Parkinson’s disease management. As advanced practice providers, we play a critical role in optimizing treatment plans and ensuring patients have access to the best available therapies," 

Association of Movement Disorder Advanced Practice Providers (AMDAPP)

 in an interview. "The long-awaited approval of ONAPGO opens another valuable tool in our clinical toolbox, giving us a new option to address motor fluctuations and improve “on” time for our patients. This therapy has the potential to be a game-changer, helping us provide more individualized and effective care to those living with Parkinson’s. Additionally, as more therapies like this are approved, it reinforces the need for continued innovation in drug development, particularly in delivering more consistent symptom control without relying solely on oral medications."

The timeline for SPN-830 dates back to September 2020, when Supernus sent its original new drug application (NDA) to the FDA.

 Shortly after, the FDA issued a refusal to file letter indicating that the NDA was not sufficiently complete to permit a substantive review. Nearly a year later, in December 2021, the company resubmitted its NDA; however, it was once again met with resistance, as the FDA 

In the CRL, the agency noted that it required additional information and analyses related to the device, including labeling, product quality and manufacturing, device performance, and risk analysis. At the time, no additional efficacy or safety clinical studies were required. Notably, the FDA mentioned in the letter that the application's approval would require inspections that could not be completed in a timely manner, primarily because of travel restrictions amid the COVID-19 pandemic.

 for SPN-830 in October 2023 which was subsequently accepted by the FDA less than a month later.

 In April 2024, the FDA issued another CRL for the device, citing 2 areas that required additional review or more information.

 The first was related to product quality while the second related to the master file for the infusion device, which is proprietary to the device manufacturer. Supernus went back to make adjustments and thus, towards the latter half of 2024, the company announced that the FDA accepted its resubmission of the NDA for SPN-830, giving it a PDUFA date of February 1, 2025.

"The approval of SPN-830 is incredibly exciting! Extensive data supports its effectiveness, as it has been used in other regions for decades—dating back 29 years in Europe. As more treatment options become available for people living with Parkinson’s disease, we, as clinicians, can better tailor treatment plans to each individual’s unique needs and best interests," Erin Zinn, MSN, APRN-CNP, ANP-BC, CMRD, director of Operations & Strategy at AMDAPP, told 

. "SPN-830 represents yet another groundbreaking option for managing PD. This is an exciting time in the movement disorders community, with new advancements offering hope for improved quality of life for those with Parkinson’s."

Updates in Therapeutic Development: Clinical Trial Readouts to Watch in the First Half of 2025

At the end of the treatment period in TOLEO, patients on SPN-830 experienced a mean reduction in OFF time of –2.47 hours per day (SD, 3.70) compared with –0.58 hours per day (SD, 2.80) for those on placebo (

 = .0025). Investigators suggested that this therapy could potentially reduce the need for higher doses of concomitant oral antiparkinsonian medications.

Additional data from the study showed that 62% of patients on SPN-830 achieved at least a 2-hour reduction in OFF time compared with 29% of those on placebo. Overall, 71% of the SPN-830 group reported improvements in their general health compared with 18% in the placebo group. Patients on the active treatment also experienced a 2.77-hour/day increase in ON time without troublesome dyskinesia and significantly improved Patient Global Impression of Change scores (

 < .001). While reductions in oral levodopa dose were not significant (

 = .0615), SPN-830 led to a significantly greater reduction in levodopa-equivalent dose than placebo (

"This therapy is particularly beneficial for patients with moderate to advanced Parkinson’s disease who struggle with unpredictable OFF periods despite optimized oral treatment, as demonstrated in the TOLEDO study. By bypassing the gastrointestinal system, ONAPGO ensures more reliable medication absorption, which is critical for those with delayed gastric emptying or erratic response to oral levodopa," Zinn explained. "As with any infusion therapy, proper patient selection, dose titration, and monitoring are essential to maximize benefits while minimizing side effects such as nausea, hypotension, and skin reactions at the infusion site. All of which we can prepare for and manage well with proper education."

Apomorphine was first approved in 2004 under the brand name Apokyn for the acute, intermittent treatment of OFF episodes in PD. Apokyn is different from SPN-830, as it is administered by subcutaneous injection with a multiple-dose pen injector that can be used up to 5 times a day, with doses no less than 2 hours apart. Apomorphine works as a dopamine agonist that binds with high affinity to the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors.

"As APPs, we play a pivotal role in educating patients, initiating therapy, titrating doses, and troubleshooting infusion management to ensure the best possible outcomes. Hands-on training and education will be key to equipping providers with the skills needed to implement this therapy effectively," Papesh said. "At AMDAPP, we are committed to supporting APPs with the education and resources needed to integrate ONAPGO into clinical practice. We will do all we can to bring hands-on training and education to the community to ensure providers feel confident using this new treatment option."

In TOLEDO, SPN-830 was generally well tolerated, with no unexpected safety concerns. Most adverse events (AEs) were mild or moderate, and no deaths occurred. TEAEs were reported in 93% of patients on SPN-830 compared with 57% on placebo, with common AEs including skin reactions, nausea, and somnolence. A higher proportion of patients in the apomorphine group experienced AEs requiring dose modification.

“The approval of a new device that delivers a drug for folks with Parkinson’s disease, using an under the skin technology, and not requiring a wire in the brain or a tube in the stomach, is a huge advantage for many folks looking to improve their Parkinson’s disease symptoms," 

 and director of the Norman Fixel Institute for Neurological Diseases, told 

 in a recent interview. “This therapy has been under development for many years and finally got over the hurdle for FDA approval. We know from studies that have been published in journals like the 

 that the number of hours of ‘good quality on medication time’ for folks with Parkinson will potentially increase about two hours. This is a meaningful change.”

Six patients in the SPN-830 group withdrew from the study due to AEs. Three of these withdrawals were due to serious events: severe hypotension, myocardial infarction, and abnormal hematology results indicating mild leucopenia and moderate anemia (non-hemolytic). The remaining three withdrawals were attributed to visual hallucinations, moderate gait disturbance, and mild infusion-site erythema. Except for myocardial infarction, all AEs leading to withdrawal were considered treatment-related and resolved after discontinuation of SPN-830.

“The pump seems to be very well tolerated, however it will likely translate in the real world to requiring some maintenance, and we therefore believe that having really great care partners, which is something important in Parkinson’s disease outcomes, will be critical for folks interested in this pump technology," Okun said in the interview with 

. “This is the second subcutaneous pump recently approved by the FDA for treatment Parkinson’s disease and is great news for many of the folks who are suffering what we refer to as motor fluctuations; where their symptoms are bouncing up and down from feeling completely off medication to experiencing, in some cases dance like movements called dyskinesia.”

 “Though we are excited to see another pump therapy, and especially one that is under the skin and less invasive than other technologies, we will crucially need to learn how to apply this pump in clinical practice. We will need to understand what persons with [Parkinson] disease will benefit the most from this therapy, and also when to pull the trigger for more aggressive therapy like deep brain stimulation or focus ultrasound," Okun explained. 

REFERENCES
1. Supernus Announces FDA Approval of ONAPGO™ (apomorphine hydrochloride) for Parkinson’s Disease. News Release. Supernus. Published February 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
2. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomized, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759. doi:10.1016/S1474-4422(18)30239-4
3. Supernus Submits NDA for SPN-830 for Continuous Treatment of ON-OFF Episodes in Adults with Parkinson’s Disease Who Have Failed Two Treatments. News release. Supernus Pharmaceuticals. September 14, 2020. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-submits-nda-spn-830-continuous-treatment-episodes
4. Supernus Resubmits NDA for SPN-830 Apomorphine Infusion Device. News release. December 8, 2021. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-resubmits-nda-spn-830-apomorphine-infusion-device
5. Supernus Provides Regulatory Update on SPN-830. News release. Supernus Pharmaceuticals. October 2022. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830
6. Supernus resubmits NDA for SPN-830 apomorphine infusion device. News release. Supernus Pharmaceuticals. October 9, 2023. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-resubmits-nda-spn-830-apomorphine-infusion-device-0
7. Supernus Provides Regulatory Update for SPN-830. News Release. Supernus Pharmaceuticals. Published April 8, 2024. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830-0
8. Supernus Announces SPN-830 Apomorphine Infusion Device NDA Accepted for Review by FDA. News release. Supernus Pharmaceuticals. August 19, 2024. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-spn-830-apomorphine-infusion-device-nda-0

Supernus Pharmaceuticals' SPN-830 (Onapgo) has been approved by the FDA as the first subcutaneous apomorphine infusion device for advanced Parkinson's disease, reducing motor fluctuations. The approval was based on the TOLEDO study, which demonstrated significant reductions in OFF time and increases in ON time without dyskinesia. Despite initial regulatory challenges, the device will be available in 2025. SPN-830 offers a non-invasive alternative to manage motor symptoms, bypassing gastrointestinal issues associated with oral medications, and providing more predictable symptom control.

SPN-830 is a wearable subcutaneous infusion device designed to deliver continuous treatment throughout the waking day, ensuring more consistent control of OFF time.

FDA Approves Apomorphine Infusion Device SPN-830 as New Parkinson Treatment

’ resubmission of its new drug application (NDA) in September 2024, the agency has approved AXS-07, an oral, rapidly absorbed, multi-mechanistic agent, as a new acute treatment of migraine with or without aura in adults. Marketed as Symbravo, the company noted that it anticipates AXS-07 to be commercially available in the United States in approximately 4 months.

AXS-07, a novel agent, is thought to act by inhibiting calcitonin gene-related peptide (CGRP) release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization. The agent, which consists of meloxicam and rizatriptan, is enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in faster absorption and longer plasma half-life.

"In terms of use in clinical practice, we want to treat our patients with the simplest, most effective acute treatments that we're able to offer them. So, you would not use a combination triptan and non-steroidal product in a patient whose treatment needs were fully met, either by a triptan alone or by a non-steroidal anti-inflammatory alone," 

, professor of neurology and director of the Montefiore Headache Center at 

 in a recent interview. "In fact, the design for individuals with unmet needs on single, monotherapy acute treatments was specifically a reflection of the fact that those are the patients who need combination therapy. I think that's something most prescribers would do and should do."

 for its NDA submission of AXS-07, citing issues related to the chemistry, manufacturing, and controls considerations. At the time, the agency did not request any new clinical trials to be conducted.

The original NDA, accepted for review in September 2021, was supported by data from 2 phase 3 randomized controlled clinical trials—the MOMENTUM trial (NCT03896009) and the INTERCEPT trial (NCT04163185). Overall, the studies revealed a statistically significant elimination of migraine pain with AXS-07 compared with placebo and active controls. 

, 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%; 

 <.001) 2 hours after dosing. Second, the absence of the most bothersome symptom (36.9%) compared with placebo (24.4%) was significant (

In MOMENTUM, 1594 patients with migraine were randomly assigned 2:2:2:1 to AXS-07, 10-mg rizatriptan, MoSEIC 20-mg meloxicam, or placebo, to treat a single migraine attack of moderate or severe intensity. INTERCEPT included 302 patients with migraine who were randomly assigned to either AXS-07 (n = 152) or placebo (n = 150) at the earliest onset of migraine pain.

 “It's always good when a new treatment is approved for migraine. This particular combination tablet is something that I've been working on as an investigator for years, so I'm delighted that it got approved, and I'm looking forward to when it becomes available in the next several months for patients for the acute treatment of migraine," 

, professor of neurology at the Geisel School of Medicine at Dartmouth and vice president of the New England Institute for Neurology and Headache, told 

 in a recent interview. "The hope is that as we educate practitioners, the understanding of why combining an [nonsteroidal anti-inflammatory drugs] with a triptan should provide additional benefit in the acute treatment of migraine for patients will become more and more clear, and that is my hope for the future."

In April 2020, months after the initial readout of MOMENTUM, Axsome announced 

. All told, the coprimary end points were also identical to MOMENTUM, with a statistically significantly greater percentage of patients achieving pain freedom compared with placebo (32.6% vs 16.3%, respectively; 

 = .002) at 2 hours post dose, as well as freedom from the most bothersome symptom (43.9% vs 26.7%, respectively; 

 = .003). AXS-07 also showed efficacy in preventing progression of migraine pain beyond mild intensity and significantly reducing the use of rescue medication, with freedom of pain progression occurring in 73.5% of AXS-07-treated patients compared with 47.4% of placebo patients between 2 and 24 hours post dose (

“Today’s approval of SYMBRAVO marks an important milestone for the migraine community by providing a rationally designed novel acute treatment for this debilitating condition. Migraine attacks strike without warning, and disrupt the lives of estimated more than 39 million patients in the U.S. alone," Herriot Tabuteau, MD, chief executive officer at Axsome Therapeutics, said in a statement.

 "SYMBRAVO provides patients and clinicians an important new option which can quickly stop a migraine attack, keep it away, and allow patients to resume their normal activities, with just a single dose. SYMBRAVO demonstrates Axsome’s commitment to developing and delivering differentiated new treatments to improve the lives of patients living with difficult to treat central nervous system disorders.”

2024 American Academy of Neurology Annual Meeting

pooled analysis of the MOMENTUM and INTERCEPT trials

, with results showing that AXS-07 was effective at acutely treating migraine. In the pooled analysis, treatment with AXS-07 resulted in greater headache pain freedom (23% vs 11%; 

<.001) and absence of the most bothersome symptom (39% vs 25%; 

<.001) at 2 hours compared with placebo. Led by Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, 43% of AXS-07-treated patients had reduced rescue medication use through 24 hours vs 21% of those on placebo (

<.001). Notably, a higher rate of patients on the investigational agent returned to normal functioning in comparison with placebo starting at 1-hour post-dose.

“Migraine is one of the most misunderstood and stigmatized neurological diseases, despite the fact that one in four households in the U.S. includes someone living with it. This widespread lack of understanding creates unnecessary barriers for individuals seeking proper diagnosis, care, and treatment," Susan Doughty, executive director of the Coalition for Headache and Migraine Patients (CHAMP), said in a statement.

 "CHAMP, alongside our 20 plus dedicated coalition organizations and patient advocates, is committed to empowering the migraine community by providing education, reducing stigma, and advocating for fair and equitable access to treatment options. The approval of SYMBRAVO as a new acute treatment for migraine is an important step forward, offering a new option for people seeking relief. We also see this moment as an opportunity to continue to shine a bright light on migraine, fostering greater awareness and helping to dismantle the stigma that so often surrounds this disease.”

REFERENCES
1. 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 January 30, 2025. https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-symbravor-meloxicam
2. Axsome Therapeutics Receives FDA Complete Response Letter for New Drug Application for AXS-07 for the Acute Treatment of Migraine. News release. Axsome Therapeutics. May 2, 2022. Accessed January 30, 2025 https://www.prnewswire.com/news-releases/axsome-therapeutics-receives-fda-complete-response-letter-for-new-drug-application-for-axs-07-for-the-acute-treatment-of-migraine-301537093.html
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 January 30, 2025. https://www.biospace.com/article/releases/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
4. Axsome Therapeutics announces AXS-07 achieves both co-primary endpoints and prevents migraine pain progression in the INTERCEPT phase 3 trial in the early treatment of migraine. news release. Axsome Therapeutics. April 6, 2020. Accessed January 30, 2025. https://www.finance.yahoo.com/news/axsome-therapeutics-announces-axs-07-100010869.html
5. Tepper S. Lipton R, Chhabra A, Streicher C, Parks G, Tabuteau H. Combined efficacy and safety of AXS-07 (MOSEICTM Meloxicam and Rizatriptan) in two phase 3 clinical trials. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. Abstract 00519

The FDA has approved AXS-07 (Symbravo), a novel oral treatment for acute migraine in adults, developed by Axsome Therapeutics. AXS-07 combines meloxicam and rizatriptan, utilizing MoSEIC technology for rapid absorption and extended plasma half-life. Clinical trials, including MOMENTUM and INTERCEPT, demonstrated significant efficacy in achieving pain freedom and reducing migraine symptoms compared to placebo. The approval addresses unmet needs in migraine treatment, offering a new option for patients with inadequate response to existing therapies. AXS-07 is expected to be available in the U.S. within four months.

Findings from previous phase 3 trial showed that treatment with AXS-07 resulted in significant reductions in headache pain freedom, migraine symptoms, and rescue medication use.

FDA Approves Axsome Therapeutics’ AXS-07 for Migraine Treatment

A recently published international survey reported that a small portion of patients with narcolepsy or idiopathic hypersomnia felt supported when adjusting to life with their condition. Published in 

the results of the survey highlighted the need for clinicians to assess social support and guide patients living with these sleep disorders toward resources that can foster community connections.

The online survey, conducted by Project Sleep

, gathered responses from 1308 adults with narcolepsy type 1 (48.4%), narcolepsy type 2 (28.7%), or idiopathic hypersomnia (22.9%). Participants were predominantly women (87.7%), White (88.8%), and under 40 years of age (68.7%). Participants represented 38 countries, with the majority (65.5%) residing in the United States, followed by 15.4% in Europe and 11.8% in Australia/New Zealand.

Adjusting to life with a diagnosis was challenging for the majority of respondents, with 67.6% rating the process as difficult or very difficult. Individuals with idiopathic hypersomnia reported greater difficulty compared with those with narcolepsy. Overall, only 32.3% of respondents felt supported in adapting to life with their condition.

"Clinicians see multiple patients with narcolepsy or idiopathic hypersomnia, but those patients don’t see or connect with each other. For those who did meet others, there was a wide range of experiences—some found social support quickly, within a few months or years, while others took much longer," lead author Julie Flygare, JD, president and CEO at Project Sleep, told  

A recent international survey highlights the challenges faced by patients with narcolepsy and idiopathic hypersomnia in finding social support. Conducted by Project Sleep, the survey involved 1308 participants, revealing that only 32.3% felt supported in adapting to their condition. Delays in diagnosis were common, with many taking over a decade to receive a diagnosis. Knowing someone with the same condition was linked to increased perceived support. The study underscores the need for healthcare providers to facilitate connections and guide patients toward supportive resources, despite privacy concerns.

In a recent survey, key factors associated with perceived support included knowing someone who had the same diagnosis of their sleep disorder, younger age, and marital status. 

Adam Numis, MD

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