Four years after winning FDA approval for Overity to treat major depressive disorder (MDD), Axum Therapeutics has launched its second U.S. approval for a first-in-class drug to treat agitation associated with dementia caused by Alzheimer’s disease.
The new approval (PDF) will keep Auvelity in competition with Lundbeck and Otsuka Pharmaceutical’s atypical antipsychotic Rexulti. Rexulti has been on the market for 10 years as a treatment for schizophrenia and MDD, and is on track to be approved for irritability in Alzheimer’s disease in 2023.
Both are oral medications, making Auvelity the first non-antipsychotic drug option for new indications. Another point of differentiation, and one in Overity’s favor, is that Rexulti carries a black box warning that it increases the risk of death in patients with dementia-related psychosis.
The New York City company’s stock rose 12% following Thursday’s approval. The company’s market capitalization now exceeds $10 billion, more than doubling since the beginning of 2025.
Auvelity targets N-methyl D-aspartate (NMDA) and sigma-1 receptors, which are thought to modulate the function of neurotransmitters implicated in Alzheimer’s disease. Decreases in certain neurotransmitters are thought to contribute to cognitive and behavioral symptoms such as agitation and aggression (PDF). Tests have shown that Auvelity works more quickly than traditional antidepressants.
Of the estimated 7 million Americans with Alzheimer’s disease, in addition to cognitive decline, up to 76% of patients report agitation, with symptoms ranging from pacing and restlessness to verbal and physical aggression.
According to Jeffrey Cummings, M.D., professor of neuroscience at UNLV Kirk Kerkorian School of Medicine, treating agitation associated with Alzheimer’s disease dementia is a critical unmet need.
“Agitation is highly prevalent in people with Alzheimer’s disease and is one of the most burdensome aspects of Alzheimer’s disease for patients and their families. Agitation in Alzheimer’s disease is associated with accelerated cognitive decline, admission to nursing homes or long-term care facilities, and increased risk of death,” Cummings said in a statement.
This approval was supported by four studies involving more than 1,000 participants. In the Advance-1 trial, Auvelity demonstrated a 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 to respond to Auvelity were divided into two groups: one continued treatment with Auvelity for six months, and the other switched to a placebo. As measured by the CMAI, patients who continued on Auvelity had a statistically significantly longer time to relapse of agitation symptoms than those who switched to placebo.
“Importantly, Overity demonstrated a convincing safety and tolerability profile, with low discontinuation rates due to adverse events and comparable to placebo,” George Grossberg, M.D., chair of geriatric psychiatry at Saint Louis University School of Medicine, said in a statement.
Axum plans to launch Overity for Alzheimer’s patients in June at the same price as the MDD indication: $1,248 for a 30-day supply before discounts and rebates.
Axsome is doing well in competition with Lundbeck and Otsuka, with Auvelity’s sales increasing 74% to $507 million last year. Meanwhile, Lundbeck reported that Rexulti’s 2025 sales rose 23% to Danish kroner 6.21 billion ($973 million).
“We’ve learned their approach,” Ari Maisel, Axum’s chief commercial offer, said of Lindbeck and Otsuka on a conference call.
“Clearly, Rexulti adopters are more likely to be Auvelity adopters. Their choices in terms of engaging with the healthcare provider and caregiver community is something we valued in shaping our launch strategy. They have done a great job and have given us great confidence in Auvelity’s market opportunity as we enter this space.”
