SHERIDAN, WYOMING – July 29, 2025 – As the Alzheimer’s treatment market evolves beyond anti-amyloid antibodies, leading biopharma companies are doubling down on symptomatic therapies to address the daily struggles of patients and caregivers. While breakthrough drugs like Leqembi and Kisunla have changed the landscape with disease-modifying potential, their limitations are propelling renewed interest in managing Alzheimer’s-related psychosis, agitation, and cognitive decline—particularly in mid-to-late-stage patients.
Repositioning Symptom Relief as an Industry Priority
With Leqembi and Kisunla indicated only for early-stage Alzheimer’s and constrained by risks such as amyloid-related imaging abnormalities (ARIA), companies including Bristol Myers Squibb (BMS), Acadia Pharmaceuticals, Lundbeck, and Otsuka are advancing a more inclusive care paradigm. These firms are reactivating and reinventing symptomatic drugs to fill therapeutic gaps left by disease-modifying approaches.
“There are many patients who are in the mid stages or more advanced stages of their disease who are experiencing debilitating symptoms,” said Ken Rhodes, Vice President of Neuroscience Research at BMS. “And those individuals need promising therapies as well.”
New Trials Target Agitation, Psychosis, and Cognitive Impairment
BMS is at the forefront with a trio of novel programs:
- Cobenfy (xanomeline + trospium): Originally studied by Eli Lilly for Alzheimer’s, this M1/M4 muscarinic combo is now in a Phase III trial (ADEPT-2) to assess its impact on psychosis in 400 Alzheimer’s patients.
- eIF2B activator: In Phase I, this candidate aims to improve cognition by rebalancing protein synthesis disrupted by amyloid and tau accumulation.
- FAAH/MAGL dual inhibitor: Now in Phase II, this asset addresses agitation by targeting the excitatory-inhibitory imbalance potentially linked to subclinical seizure activity.
Similarly, Acadia is testing ACP-204, a 5-HT2A inverse agonist derived from its Parkinson’s drug Nuplazid, in a Phase II study for Alzheimer’s psychosis, with plans for additional trials in Lewy body dementia.
A Continuum of Care for a Growing Global Burden
These initiatives align with industry consensus that Alzheimer’s therapy must extend beyond disease modification to practical, quality-of-life improvements. With over 55 million people living with dementia globally—a figure expected to rise to 78 million by 2030—demand for diverse, stage-appropriate treatments is surging.
“Whilst memory loss is upsetting and difficult, the psychosis and other areas . . . including agitation, they’re really, really disturbing for families,” said Catherine Owen Adams, CEO of Acadia Pharmaceuticals. “It means that caring for that patient becomes incredibly hard at home.”
Reclaimed Assets and Class Warnings
The repositioning of psychiatric drugs for Alzheimer’s is not without hurdles. Rexulti, approved by FDA in 2023 for Alzheimer’s-related agitation, carries a boxed warning due to elevated mortality risk in elderly dementia patients—a legacy from its classification as an atypical antipsychotic. Still, regulators and developers are weighing risk-benefit profiles in favor of much-needed relief.
Other companies eyeing the symptomatic space include:
- AbbVie, now developing emraclidine—acquired from Cerevel Therapeutics—for Alzheimer’s psychosis after its initial failure in schizophrenia.
- Neumora Therapeutics, currently testing NMRA-511, a vasopressin 1a receptor antagonist, in a Phase I study for agitation.
Disease Modification Remains in Parallel Focus
While symptomatics regain traction, work on next-generation disease-modifying therapies continues. BMS’s tau-directed antibody program is progressing through Phase II as the company seeks to address neurofibrillary tangle pathology without the ARIA risk seen with amyloid therapies.
Meanwhile, Eli Lilly is attempting to reduce ARIA incidence for Kisunla through gradual dosing and is conducting its TRAILBLAZER-ALZ 3 trial in pre-symptomatic patients, with results due in 2027. Novo Nordisk’s EVOKE and EVOKE Plus studies may provide a faster verdict on GLP-1 potential in Alzheimer’s, with data expected in September.
Strategic Outlook: A Tipping Point for Alzheimer’s Therapeutics
Industry leaders agree that Alzheimer’s drug development is entering a new phase—defined by integration rather than opposition between symptomatic and disease-modifying approaches. This dual focus may be the key to delivering measurable relief across all disease stages.
“I can confidently say that we’re really at a tipping point of bringing forward potentially transformational therapies in Alzheimer’s disease,” Rhodes affirmed.
Learn more at https://www.bms.com