FDA Pre-NDA Meeting for AXS-05 in Alzheimer's Disease Sets Stage for sNDA Submission in Q3 2025

Axsome Therapeutics has received formal pre-New Drug Application (NDA) meeting minutes from the FDA, confirming that its planned supplemental NDA (sNDA) submission for AXS-05 (dextromethorphan-bupropion) in Alzheimer’s disease agitation is supported by existing clinical and nonclinical data.

Axsome expects to submit the investigational oral combination for FDA review in the third quarter of 2025.

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If approved, AXS-05 would offer a novel mechanism of action for a condition with limited treatment options. The FDA previously granted AXS-05 Breakthrough Therapy designation for Alzheimer’s disease agitation in June 2020, making the application eligible for Priority Review.

“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,” Herriot Tabuteau, MD, chief executive officer of Axsome said in a news release. "Alzheimer’s disease agitation is a serious, distressing, and prevalent condition with limited treatment options." Approval of AXS-05 has the potential to address "a high unmet medical need,” Tabuteau continued.

The clinical development program for AXS-05 in Alzheimer’s disease agitation comprises 4 completed pivotal, phase 3, placebo-controlled efficacy trials, along with a long-term safety study. In 3 efficacy trials—ADVANCE-1, ACCORD-1, and ACCORD-2—AXS-05 demonstrated statistically significant improvement in agitation symptoms based on the Cohen-Mansfield Agitation Inventory, (P =.010, P =.014, and P =.001, respectively). A fourth trial, ADVANCE-2, supported additional controlled safety and efficacy data. Long-term safety evaluation of AXS-05 included more than 300 adults treated for at least 6 months and more than 100 participants treated for at least 12 months, according to Axsome. Results demonstrated good tolerability and no increased risk of falls, sedation, or cognitive decline, as measured by the Mini-Mental State Examination. There were no deaths reported among AXS-05-treated trial participants.

Alzheimer’s disease is the most common form of dementia and affects approximately 7 million people in the United States, according to the Alzheimer's Disease Foundation.2 Agitation occurs in up to 70% of individuals with the disorder and is associated with significant morbidity, including accelerated cognitive decline, increased caregiver burden, earlier nursing home placement, and higher mortality rates. Currently, treatment options for Alzheimer’s disease agitation remain limited.

AXS-05 is a proprietary combination of dextromethorphan and bupropion in which dextromethorphan acts as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion increases the bioavailability of dextromethorphan and serves as a norepinephrine and dopamine reuptake inhibitor. The drug is covered by a patent estate extending until at least 2043 and is also in development for smoking cessation.