Axsome Therapeutics Announces Positive Outcome of Interim Analysis of ADVANCE-1 Phase 2/3 Trial of AXS-05 in Alzheimer’s Disease Agitation
IDMC recommends continuation of trial evaluating AXS-05 versus placebo in Alzheimer’s disease agitation
IDMC recommends no further enrollment to single-agent bupropion arm
AXS-05 is a novel, oral, investigational medicine consisting of dextromethorphan and bupropion. Patients in the ADVANCE-1 trial were being randomized in a 1:1:1 ratio to treatment with AXS-05, placebo, or bupropion. The primary endpoint of the study is the change in the Cohen Mansfield Agitation Inventory (CMAI) for AXS-05 as compared to placebo. The single-agent bupropion arm of the study was included to compare the efficacy of AXS-05 to the bupropion component, with the goal of demonstrating the superiority of AXS-05, as required by the
“The positive recommendation by the IDMC to continue the ADVANCE-1 trial is an important milestone for the Alzheimer’s disease agitation program and we look forward to the continued development of AXS-05 for this indication,” said
AXS-05 combines glutamatergic, monoaminergic and anti-inflammatory mechanisms of action, and Axsome’s proprietary metabolic inhibition technology. Pharmacokinetic data from Phase 1 trials of AXS-05 and clinical observations with the dextromethorphan component indicate that AXS-05 increases dextromethorphan concentrations into a potentially therapeutic range. AXS-05 has been granted FDA Fast Track designation for the treatment of AD agitation.
“Agitation is reported in up to 70% of Alzheimer’s disease patients, is highly distressing for patients and their caregivers, and is associated with significant negative outcomes, including earlier institutionalization and increased mortality,” said Cedric O’Gorman, MD, Senior Vice President of Clinical Development and Medical Affairs of Axsome. “There is currently no approved treatment for Alzheimer’s disease agitation. The significant clinical impact of this unmet medical need underscores the importance of the ADVANCE-1 trial in evaluating the potential of AXS-05 to treat this serious indication.”
About the ADVANCE-1 Study
ADVANCE-1 (Addressing Dementia Via Agitation-Centered Evaluation 1) is a Phase 2/3 multicenter, randomized, double-blind, controlled trial to evaluate the efficacy and safety of AXS-05 in patients with agitation associated with Alzheimer’s disease. Approximately 435 patients were to be randomized in a 1:1:1 ratio to receive AXS-05, bupropion, or placebo for 5 weeks. The primary efficacy measure is the Cohen-Mansfield Agitation Inventory (CMAI). The trial incorporates two interim analyses to be performed by an independent data monitoring committee. The first interim analysis was performed on the first approximately 30% of the target number of subjects to assess futility. The second interim analysis is anticipated to be performed on the first approximately 60% of the target number of subjects to assess efficacy.
About Alzheimer’s Disease (AD) Agitation
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that manifests initially as forgetfulness advancing to severe cognitive impairment and memory loss. It afflicts an estimated 5 million individuals in
AXS-05 is a novel, oral, investigational drug product under development for the treatment of central nervous system (CNS) disorders. AXS-05 consists of bupropion and dextromethorphan and utilizes Axsome’s metabolic inhibition technology. Dextromethorphan is an NMDA receptor antagonist, sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, and inhibitor of the serotonin and norepinephrine transporters. Bupropion serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 is an investigational drug product not approved by the FDA. The safety and efficacy of AXS-05 have not yet been established.
Forward Looking Statements
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Source: Axsome Therapeutics, Inc.