Axsome Submits FDA Application for AXS-05 in Alzheimer's Disease Agitation Following Positive Phase 3 Results
核心洞察
Axsome Therapeutics has submitted a supplemental NDA to the FDA for AXS-05 (dextromethorphan-bupropion) to treat agitation (搜索) associated with Alzheimer's disease (搜索), addressing a critical unmet medical need affecting millions of patients.
The ACCORD-2 phase 3 study demonstrated that AXS-05 met its primary efficacy endpoint and showed a tolerable safety profile for treating Alzheimer's disease (搜索) agitation (搜索).
Previous pivotal ADVANCE-1 trial results showed AXS-05 achieved a statistically significant 15.4-point reduction in agitation (搜索) scores compared to 11.5 points for placebo, with the drug being well-tolerated without cognitive impairment or sedation.
Axsome Therapeutics has submitted a supplemental New Drug Application (sNDA) to the FDA for AXS-05 (dextromethorphan-bupropion) for the treatment of agitation (搜索) associated with Alzheimer's disease (搜索), following positive results from the phase 3 ACCORD-2 study. The submission addresses what the company describes as "a serious condition affecting millions of patients in the US, and a critical unmet medical need."
Phase 3 ACCORD-2 Study Results
The ACCORD-2 phase 3 study evaluated AXS-05 for treating agitation (搜索) associated with Alzheimer's disease (搜索) and met its primary endpoint for efficacy while demonstrating a tolerable safety profile. According to George T. Grossberg, MD, the Henry & Amelia Nasrallah professor and director of the division of geriatric psychiatry in the department of psychiatry and behavioral neuroscience at St. Louis University School of Medicine, the findings support AXS-05 as "an appropriate, safe and well-tolerated treatment of agitation associated with Alzheimer's disease."
Previous Pivotal Trial Data
The FDA submission is supported by robust data from the pivotal phase 2/3 ADVANCE-1 study, a randomized, double-blind, controlled, multicenter US trial that enrolled 366 participants with Alzheimer's disease (搜索). In this study, participants received AXS-05, bupropion, or placebo.
AXS-05 demonstrated statistically significant efficacy on the primary endpoint, achieving a mean reduction of 15.4 points from baseline in the Cohen Mansfield Agitation (搜索) Inventory (CMAI) total score compared to 11.5 points for placebo at week 5 (P=0.010). The treatment also proved superior to bupropion alone on the CMAI total score (P <0.001), establishing component contribution.
Safety Profile
The safety analysis from ADVANCE-1 showed that AXS-05 was well tolerated and notably was not associated with cognitive impairment or sedation. The most commonly reported adverse events in the AXS-05 arm were somnolence (8.2% for AXS-05 vs 4.1% for bupropion and 3.2% for placebo), dizziness (6.3%, 10.2%, 3.2%, respectively), and diarrhea (4.4%, 6.1%, 4.4%, respectively).
Drug Mechanism and Regulatory Status
AXS-05 is a novel, oral, investigational N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 (搜索) agonist, and aminoketone CYP2D6 (搜索) inhibitor. The drug received FDA Breakthrough Therapy designation for Alzheimer's disease (搜索) agitation (搜索) in 2020, marking the second such designation for AXS-05, with the first being granted for major depressive disorder.
Broader Development Pipeline
Beyond Alzheimer's disease (搜索) agitation (搜索), Axsome is developing AXS-05 for smoking cessation, with plans to initiate a pivotal phase 2/3 trial in late 2025. Research data shows that AXS-05 significantly reduced daily smoking compared with bupropion, with a 25% greater decrease in the average number of cigarettes smoked each day over a 3-week period. Patients receiving AXS-05 had an average reduction of 8.49 cigarettes per day, compared with a 6.79 reduction for patients receiving bupropion.
"Our broad development pipeline continues to advance, and we recently submitted our supplemental NDA for AXS-05 for the treatment of Alzheimer disease agitation (搜索)," said Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics. "With robust commercial performance and pipeline execution, Axsome is well positioned to continue delivering substantial and sustained growth and transformative new medicines for patients living with serious CNS disorders."