Previously completed positive, pivotal ADVANCE-1 trial sufficient with single additional Phase 3 efficacy trial for NDA in Alzheimer’s disease agitation
Initiation of Phase 3, placebo-controlled, randomized-withdrawal efficacy trial on track for 4Q 2020
Initiation of long-term safety trial in patients with Alzheimer’s disease agitation expected in 4Q 2020
No treatments are currently approved for the treatment of Alzheimer’s disease agitation
NEW YORK, Aug. 31, 2020 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, today announced confirmation of the pivotal development status and plan for AXS-05 in the treatment of Alzheimer’s disease (AD) agitation following a successful Breakthrough Therapy meeting with the U.S. Food and Drug Administration (FDA). AXS-05 (dextromethorphan/bupropion modulated delivery tablet) is a novel, oral, investigational NMDA receptor antagonist and sigma-1 receptor agonist. There is currently no approved treatment for AD agitation.
Results of the meeting confirm the pivotal status of the previously completed positive ADVANCE-1 trial, and the establishment of the superiority of AXS-05 over its components (component contribution) in the treatment of AD agitation. Consequently, only one additional Phase 3 efficacy trial will be needed to support the filing of an NDA (New Drug Application) for approval of AXS-05 in this indication, and only a placebo control will be required for this trial. This additional Phase 3 efficacy trial will be conducted using a randomized-withdrawal design, in which all patients are first treated with open-label AXS-05, with the patients experiencing a treatment response being subsequently randomized in a double-blind fashion to continued treatment with AXS-05 or to switch to placebo. Axsome is on track to initiate this efficacy trial in the fourth quarter of 2020. Axsome also intends to initiate in the fourth quarter an open-label safety extension trial of AXS-05 in AD agitation patients to supplement the existing AXS-05 long-term safety database.
“Axsome is very pleased with the FDA feedback from our recent Breakthrough Therapy meeting, which confirms a streamlined path to NDA submission for AXS-05 in Alzheimer’s disease agitation, including the pivotal status of our completed ADVANCE-1 trial and the need for only one additional placebo-controlled efficacy trial,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “The randomized-withdrawal design of this additional Phase 3 trial may simultaneously improve signal detection and mitigate placebo response. We remain on track to initiate this trial before year end. Alzheimer’s disease agitation is very distressing to patients and their families, and is associated with earlier nursing home placement, accelerated progression to severe dementia, and increased risk of death. If successfully developed, AXS-05 has the potential to address this serious, prevalent, and debilitating condition, for which there is currently no approved treatment.”
In June 2020, Axsome received Breakthrough Therapy designation from the FDA for AXS-05 for the treatment of AD agitation, the second Breakthrough Therapy designation received by Axsome for AXS-05. 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