FDA cleared Auvelity for agitation in patients with Alzheimer’s dementia, making it the first non-antipsychotic drug cleared for this indication.
Axsome’s stock jumped nearly 13% Thursday, closing at $207.75. William Blair analysts see peak sales topping $2.1 billion in this indication alone.
The drug combines dextromethorphan, an NMDA receptor blocker, and bupropion, an atypical antidepressant. It was first cleared in August 2022 for major depressive disorder and generated $507 million in 2025 sales.
The approval was based on the ADVANCE and ACCORD-2 studies, though the data were mixed. ACCORD-2 hit its primary endpoint: a 3.6-fold lower risk of agitation relapse versus placebo. It also improved agitation severity scores.
ADVANCE-2, though, couldn’t outperform placebo at easing agitation. Axsome pushed through on the strength of two earlier positive readouts: ACCORD-1 in 2022, which delayed time to relapse, and ADVANCE-1 in 2020, which improved agitation scores versus placebo.
Axsome now faces Otsuka and Lundbeck, whose Rexulti was cleared for Alzheimer’s agitation in 2023 and generated $973 million in 2025 sales. Rexulti holds only around 4.6% market share, meaning the indication is wide open, William Blair wrote.
There’s also a clinical angle. Rexulti carries a black-box warning for mortality in elderly patients experiencing psychosis, a condition with high comorbidity overlap with agitation. A non-antipsychotic alternative matters.
Auvelity carries its own boxed warning for suicidal thoughts and behaviors.
Sarah Chen