Axsome Therapeutics Announces FDA Pre-NDA Meeting Minutes for AXS-05 in Alzheimer’s Disease Agitation Supporting NDA Submission
Axsome Therapeutics (NASDAQ: AXSM) has received FDA pre-NDA meeting minutes supporting a supplemental New Drug Application (sNDA) submission for AXS-05 in treating Alzheimer's disease agitation. The submission is planned for Q3 2025.
AXS-05, granted Breakthrough Therapy designation in June 2020, demonstrated significant improvement in three Phase 3 trials: ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014), and ACCORD-2 (p=0.001). The drug's development program includes four Phase 3 efficacy trials and a long-term safety trial.
Safety studies involving over 300 patients treated for 6+ months and 100+ patients for 12+ months showed AXS-05 was well-tolerated, with no deaths reported and no increased risk of falls, sedation, or cognitive decline.
Axsome Therapeutics (NASDAQ: AXSM) ha ricevuto il verbale dell'incontro pre-NDA della FDA che supporta la presentazione di una domanda di approvazione di farmaco supplementare (sNDA) per AXS-05 nel trattamento dell'agitazione associata alla malattia di Alzheimer. La presentazione è prevista per il terzo trimestre del 2025.
AXS-05, che ha ricevuto la designazione di Terapia Innovativa a giugno 2020, ha dimostrato un miglioramento significativo in tre studi di fase 3: ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014) e ACCORD-2 (p=0.001). Il programma di sviluppo del farmaco include quattro studi di efficacia di fase 3 e uno studio di sicurezza a lungo termine.
Studi di sicurezza che hanno coinvolto oltre 300 pazienti trattati per più di 6 mesi e oltre 100 pazienti per più di 12 mesi hanno mostrato che AXS-05 è stato ben tollerato, senza decessi segnalati e senza aumento del rischio di cadute, sedazione o declino cognitivo.
Axsome Therapeutics (NASDAQ: AXSM) ha recibido el acta de la reunión pre-NDA de la FDA que respalda la presentación de una solicitud de nuevo medicamento suplementario (sNDA) para AXS-05 en el tratamiento de la agitación asociada a la enfermedad de Alzheimer. Se planea la presentación para el tercer trimestre de 2025.
AXS-05, que recibió la designación de Terapia Innovadora en junio de 2020, demostró una mejora significativa en tres ensayos de fase 3: ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014) y ACCORD-2 (p=0.001). El programa de desarrollo del fármaco incluye cuatro ensayos de eficacia de fase 3 y un ensayo de seguridad a largo plazo.
Los estudios de seguridad que involucraron a más de 300 pacientes tratados durante más de 6 meses y a más de 100 pacientes durante más de 12 meses mostraron que AXS-05 fue bien tolerado, sin muertes reportadas y sin aumento del riesgo de caídas, sedación o deterioro cognitivo.
Axsome Therapeutics (NASDAQ: AXSM)는 알츠하이머병의 불안 증세 치료를 위한 AXS-05의 보충 신약 신청(sNDA) 제출을 지원하는 FDA의 NDA 사전 회의록을 받았습니다. 제출은 2025년 3분기로 예정되어 있습니다.
AXS-05는 2020년 6월 혁신 치료제로 지정되었으며, ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014), ACCORD-2 (p=0.001)라는 세 가지 3상 시험에서 유의미한 개선을 보여주었습니다. 이 약물의 개발 프로그램에는 네 개의 3상 효능 시험과 장기 안전성 시험이 포함됩니다.
6개월 이상 치료받은 300명 이상의 환자와 12개월 이상 치료받은 100명 이상의 환자를 포함한 안전성 연구에서 AXS-05는 잘 견뎌졌으며, 사망 보고가 없었고 낙상, 진정 또는 인지 저하의 위험이 증가하지 않았습니다.
Axsome Therapeutics (NASDAQ: AXSM) a reçu le compte-rendu de la réunion pré-NDA de la FDA soutenant la soumission d'une demande de médicament nouveau supplémentaire (sNDA) pour AXS-05 dans le traitement de l'agitation liée à la maladie d'Alzheimer. La soumission est prévue pour le troisième trimestre 2025.
AXS-05, qui a reçu la désignation de Thérapie Innovante en juin 2020, a montré une amélioration significative dans trois essais de phase 3 : ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014) et ACCORD-2 (p=0.001). Le programme de développement du médicament comprend quatre essais d'efficacité de phase 3 et un essai de sécurité à long terme.
Des études de sécurité impliquant plus de 300 patients traités pendant plus de 6 mois et plus de 100 patients pendant plus de 12 mois ont montré qu'AXS-05 était bien toléré, sans décès signalés et sans augmentation du risque de chutes, de sédation ou de déclin cognitif.
Axsome Therapeutics (NASDAQ: AXSM) hat das Protokoll des FDA-Pre-NDA-Meetings erhalten, das die Einreichung eines Antrags auf zusätzliche Arzneimittelzulassung (sNDA) für AXS-05 zur Behandlung der Unruhe bei Alzheimer-Krankheit unterstützt. Die Einreichung ist für das dritte Quartal 2025 geplant.
AXS-05, das im Juni 2020 den Status eines Durchbruchstherapies erhalten hat, zeigte in drei Phase-3-Studien signifikante Verbesserungen: ADVANCE-1 (p=0.010), ACCORD-1 (p=0.014) und ACCORD-2 (p=0.001). Das Entwicklungsprogramm des Medikaments umfasst vier Phase-3-Wirksamkeitsstudien und eine langfristige Sicherheitsstudie.
Sicherheitsstudien mit über 300 Patienten, die mehr als 6 Monate behandelt wurden, und über 100 Patienten, die mehr als 12 Monate behandelt wurden, zeigten, dass AXS-05 gut verträglich war, ohne berichtete Todesfälle und ohne erhöhtes Risiko für Stürze, Sedierung oder kognitive Beeinträchtigungen.
- FDA supports sNDA submission for AXS-05
- Breakthrough Therapy designation enables Priority Review
- Positive efficacy results in three Phase 3 trials
- Strong safety profile with no significant adverse effects
- Addresses high unmet medical need in Alzheimer's agitation
- sNDA submission not until Q3 2025
- Final FDA acceptance still pending review
Insights
Axsome's FDA pre-NDA meeting outcome represents a significant regulatory milestone for AXS-05 in Alzheimer's disease agitation. The FDA's confirmation that Axsome's regulatory package is sufficient for sNDA submission substantially reduces regulatory uncertainty and establishes a clear pathway to potential approval. The Breakthrough Therapy designation and eligibility for Priority Review are particularly noteworthy, as they could accelerate the review timeline from the standard 10 months to approximately 6 months after submission.
The company's Q3 2025 submission timeline provides investors with a concrete regulatory catalyst. With four completed Phase 3 trials showing statistically significant improvements in the Cohen-Mansfield Agitation Inventory and robust long-term safety data, Axsome has assembled a comprehensive data package that addresses both efficacy and safety requirements for approval consideration.
The Alzheimer's disease agitation market represents a substantial commercial opportunity with treatment options. Current approaches often rely on off-label use of antipsychotics that carry black box warnings. AXS-05's novel mechanism as an NMDA receptor antagonist and sigma-1 agonist could position it as a differentiated therapy with potentially fewer safety concerns, as evidenced by the absence of increased risk of falls, sedation, or cognitive decline in long-term studies.
The clinical data package for AXS-05 in Alzheimer's disease agitation appears remarkably robust. Having three positive Phase 3 trials demonstrating statistically significant improvements on the Cohen-Mansfield Agitation Inventory is exceptional in CNS drug development, where replication of positive findings is often challenging. The combination of both traditional parallel-group trials (ADVANCE-1) and randomized withdrawal studies (ACCORD-1 and ACCORD-2) provides complementary evidence of efficacy using different trial designs.
The safety profile is particularly encouraging for an Alzheimer's population. The absence of increased risks for falls, sedation, and cognitive decline addresses key concerns with current treatment approaches. The extensive long-term safety database with over 300 patients treated for 6+ months and 100+ patients for 12+ months exceeds typical requirements for chronic-use drugs in this population.
AXS-05's mechanism as a dextromethorphan-bupropion combination represents a novel approach. The NMDA receptor antagonism and sigma-1 agonism target neurobiological pathways implicated in agitation, while the bupropion component inhibits CYP2D6, effectively boosting dextromethorphan exposure. This differentiated mechanism could potentially offer efficacy without the adverse effects associated with antipsychotics currently used off-label, positioning AXS-05 as a potential first-line option if approved.
Supplemental New Drug Application (sNDA) submission anticipated in 3Q 2025
NEW YORK, March 03, 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 it has received formal pre-New Drug Application (NDA) meeting minutes from the U.S. Food and Drug Administration (FDA) supporting a supplemental NDA (sNDA) submission for AXS-05 in Alzheimer’s disease agitation. AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor. The purpose of the meeting was to reach agreement with the FDA on the proposed content and format of the Company’s planned sNDA submission including the clinical and nonclinical requirements.
Based on the feedback from the FDA, the Company’s regulatory data package would be sufficient for the submission of an sNDA for AXS-05 for the treatment of Alzheimer’s disease agitation. Axsome anticipates submitting the planned sNDA in the third quarter of 2025. Acceptance of the final sNDA will be subject to the FDA’s review of the complete filing. AXS-05 was granted Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020.
“We are pleased with the pre-NDA meeting feedback we received from the FDA, which confirmed the studies and data to be presented in our planned sNDA submission of AXS-05 for the treatment of Alzheimer’s disease agitation,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Alzheimer’s disease agitation is a serious, distressing, and prevalent condition with limited treatment options. If approved, AXS-05 would represent a new mechanism of action for the treatment of Alzheimer’s disease agitation with the potential to address this high unmet medical need. As an FDA Breakthrough Therapy designated program, the application for AXS-05 will be eligible for Priority Review. We look to complete the sNDA submission in the third quarter of 2025, with the goal of making this important new potential therapy available to patients living with Alzheimer’s disease as quickly as possible.”
The comprehensive clinical development program of AXS-05 in Alzheimer’s disease agitation includes four completed pivotal, Phase 3, placebo-controlled efficacy trials, and a completed long-term safety trial. AXS-05 demonstrated statistically significant improvement in Alzheimer’s disease agitation, assessed using the Cohen-Mansfield Agitation Inventory (CMAI), compared to placebo, in three Phase 3 efficacy trials: the ADVANCE-1 parallel-group trial (p=0.010), the ACCORD-1 randomized withdrawal trial (p=0.014), and the ACCORD-2 randomized withdrawal trial (p=0.001). Additional controlled safety and supportive efficacy results are provided by a fourth trial (ADVANCE-2). The long-term safety and tolerability of AXS-05 was also evaluated in more than 300 patients treated for at least 6 months and more than 100 patients treated for at least 12 months. AXS-05 was well tolerated with long-term dosing. There were no deaths in patients receiving AXS-05 and AXS-05 was not associated with increased risk of falls, sedation, or cognitive decline as assessed by the Mini-Mental State Examination (MMSE).
About Alzheimer’s Disease Agitation
Alzheimer’s disease (AD) is the most common form of dementia, affecting approximately 7 million people in the United States.1 Agitation is reported in up to
About AXS-05
AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 agonist, and aminoketone CYP2D6 inhibitor under development for the treatment of Alzheimer’s disease (AD) agitation and smoking cessation. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is covered by a robust patent estate extending out to at least 2043. AXS-05 was granted U.S. FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020.
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. For more information, please visit the Company’s website at www.axsome.com.
Forward Looking Statements
Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s Sunosi®, Auvelity®, and Symbravo® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of Sunosi, Auvelity, and Symbravo and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.
Investors:
Mark Jacobson
Chief Operating Officer
(212) 332-3243
mjacobson@axsome.com
Media:
Darren Opland
Director, Corporate Communications
(929) 837-1065
dopland@axsome.com
References
- Alzheimer’s Association. 2024 Alzheimer’s Disease Facts and Figures.
- Tractenburg, R.E. et al. Estimating the prevalence of agitation in community-dwelling persons with Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2002 Winter;14(1):11-8.
- Porsteinsson, A.P. and Antonsdottir, I.M. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2017 Apr;18(6):611-620.
FAQ
When will Axsome submit the sNDA for AXS-05 in Alzheimer's disease agitation?
What clinical trial results did AXSM's AXS-05 achieve in Alzheimer's agitation?
How many patients were included in AXS-05's long-term safety studies?
What safety profile did AXS-05 demonstrate in Alzheimer's agitation trials?
When did AXSM receive Breakthrough Therapy designation for AXS-05?
