Four years after gaining FDA approval for Auvelity to treat major depressive disorder (MDD), Axsome Therapeutics has tacked on a second nod in the United States for the first-in-class medicine to treat agitation associated with dementia caused by Alzheimer’s disease.
With the new endorsement (PDF), Auvelity will continue its competition with Lundbeck and Otsuka’s atypical antipsychotic Rexulti, which has been on the market for a decade to treat schizophrenia and MDD and secured its nod for Alzheimer’s agitation in 2023.
Both are oral medications, with Auvelity becoming the first non-antipsychotic option in its new indication. Another point of differentiation—and one which favors Auvelity—is that Rexulti carries a black box warning for posing a higher risk of mortality for those with dementia-related psychosis.
With the approval on Thursday, shares in the New York City company jumped by 12%. The company’s market cap now sits above $10 billion, having more than doubled since the start of 2025.
Auvelity targets the N-methyl D-aspartate (NMDA) and sigma-1 receptors, which are believed to modulate the function of neurotransmitters implicated in Alzheimer’s disease. Reductions in certain neurotransmitters are thought to contribute to cognitive and behavioral symptoms, including agitation and aggression, Axsome noted (PDF). In trials, Auvelity has been shown to work more rapidly than traditional antidepressants.
Of the estimated 7 million Americans who have Alzheimer’s disease, in addition to cognitive decline, agitation is reported in up to 76% of patients with symptoms ranging from pacing or restlessness to verbal and physical aggression.
Treatment for agitation associated with Alzheimer’s disease dementia has been a critical unmet need, according to Jeffrey Cummings, M.D., a professor of brain sciences at the UNLV Kirk Kerkorian School of Medicine.
“Agitation is highly prevalent in patients with Alzheimer's disease and among the most burdensome aspects of the disease for patients and families. Alzheimer's disease agitation is associated with accelerated cognitive decline, placement in assisted living and long-term care facilities, and increased mortality risk,” Cummings said in a release.
The approval was backed by four studies, which included more than 1,000 participants. In the Advance-1 trial, Auvelity demonstrated statistically significant improvement in agitation symptoms compared to placebo as measured by the Cohen-Mansfield Agitation Inventory (CMAI) total score at Week 5.
In the Accord-2 trial, patients who were known responders to Auvelity were split into two groups, with one continuing treatment with Auvelity for six months and another switching to placebo. Patients who continued with Auvelity experienced a statistically significantly longer time to relapse of agitation symptoms, measured by the CMAI, than those who switched to placebo.
“Importantly, Auvelity showed a compelling safety and tolerability profile, with rates of discontinuation due to adverse events that were low and matched those of placebo,” George Grossberg, M.D., the Director of the Division of Geriatric Psychiatry at the Saint Louis University School of Medicine, said in the release.
Axsome expects to launch Auvelity for Alzheimer’s patients in June and will charge the same price that it does for its MDD indication, which is $1,248 for a 30-day supply before discounts and rebates.
Axsome has fared well in its competition with Lundbeck and Otsuka as Auvelity generated sales of $507 million last year, up 74%. Meanwhile, Lundbeck reported 2025 sales of Rexulti at 6.21 billion Danish kroner ($973 million), which were up by 23%.
“We’ve been students of their approach,” Ari Maizel, Axsome’s chief commercial officer, said of Lindbeck and Otsuka during a conference call.
“Obviously, the adopters of Rexulti are likely adopters of Auvelity. Their choices in terms of engagement with healthcare providers and the caregiver community have been things we’ve evaluated to form our launch strategy. They’ve done a nice job and given us a lot of confidence in the market opportunity for Auvelity as we enter the space.”