Axsome Therapeutics Receives FDA Breakthrough Therapy Designation for AXS-05 for the Treatment of Alzheimer’s Disease Agitation

Saturday, June 27, 2020

Axsome Therapeutics, Inc., a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for AXS-05 for the treatment of Alzheimer’s disease (AD) agitation. AXS-05 is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. This is the second Breakthrough Therapy designation granted to Axsome for AXS-05. There is currently no approved treatment for AD agitation.

A Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition. The Breakthrough Therapy designation for AXS-05 in AD agitation was supported by the recent positive results from the pivotal Phase 2/3 ADVANCE-1 study, a randomized, double-blind, controlled, multicenter U.S. trial in which 366 Alzheimer’s disease patients were treated with AXS-05, bupropion, or placebo. In this trial, treatment with AXS-05 resulted in a rapid, substantial, and statistically significant improvement in agitation as compared to placebo. On the primary endpoint, AXS-05 demonstrated a statistically significant mean reduction from baseline in the Cohen Mansfield Agitation Inventory (CMAI) total score compared to placebo at Week 5, with mean reductions of 15.4 points for AXS-05 and 11.5 points for placebo (p=0.010). AXS-05 was also superior to bupropion on the CMAI total score (p<0.001), establishing component contribution. AXS-05 was well tolerated and 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 versus 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).

“This FDA Breakthrough Therapy designation is an important milestone in the development of AXS-05 for Alzheimer’s disease agitation, a serious, prevalent, and debilitating condition for which there is currently no approved therapy,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “This marks the second Breakthrough Therapy designation received by Axsome for AXS-05, the first being for the treatment of major depressive disorder, and highlights the potential of AXS-05 to address unmet medical needs in multiple difficult-to-treat CNS disorders. We look forward to working with the FDA over the coming months as we advance the development of AXS-05 for the treatment of Alzheimer’s disease agitation.”