Targeting Psychosis in Alzheimer’s Disease

This episode of The BioReport explores the overlooked yet critical challenge of psychosis in Alzheimer's disease, focusing on its profound impact on patients and caregivers. Host Daniel Levine interviews Elizabeth Thompson, Executive Vice President and Head of R&D at Acadia Pharmaceuticals, who explains that hallucinations and delusions—afflicting up to 30% of Alzheimer’s patients—are not merely symptoms of cognitive decline but distinct drivers of functional deterioration, safety risks, and premature nursing home placement. Thompson emphasizes that current treatments, largely off-label antipsychotics, come with significant trade-offs like worsened motor function and cognition. Acadia is advancing remlefanserin (formerly ACP204), a next-generation 5-HT2A inverse agonist designed specifically to treat Alzheimer’s psychosis without these side effects. The drug builds on the foundation of Nuplazid (pimavanserin), with improvements including a reduced risk of QT prolongation, faster onset of action, and potential for higher dosing to enhance efficacy. Phase II trials are underway, with primary endpoints focused on hallucinations and delusions, and a biomarker-confirmed Alzheimer’s diagnosis required for enrollment. The episode also discusses broader shifts in neurology drug development, including increased investment, clinical progress, and evolving deal structures, all signaling a maturing field poised for meaningful innovation. Thompson underscores that treating psychosis is not just a medical intervention but a lifeline for families, potentially delaying institutionalization and reducing caregiver burden. She highlights the importance of designing trials with real-world impact in mind—focusing on patient and caregiver needs from the outset. With growing confidence in Alzheimer’s biology and biomarker tools, the industry is moving beyond cognitive decline as the sole target. The episode concludes with a forward-looking perspective on global commercialization, acknowledging regional disparities in diagnosis, reimbursement, and care standards, and the need to raise the bar everywhere. Ultimately, remlefanserin represents a paradigm shift: treating psychosis as a distinct, addressable condition in dementia, not just a side effect of disease progression.