Delay on Cobenfy Alzheimer Disease Psychosis Data Following Phase 3 Study “Irregularities,” New Patients Enrolled

Bristol Myers Squibb today announced that it will enroll additional patients in the ADEPT-2 study—a phase 3, multicenter, randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of xanomeline/trospium (Cobenfy) in participants with psychosis associated with Alzheimer disease dementia.¹

Following a thorough blinded review of the ADEPT-2 study data, BMS identified irregularities due to clinical trial execution at a limited number of study sites. After reviewing these findings and before a database lock, BMS decided to exclude the patient data from those select sites from the primary analysis. BMS then consulted with the US Food and Drug Administration (FDA); jointly, they came to an agreement that an interim data analysis for efficacy and safety should be conducted by an independent party and then reviewed by the Data Monitoring Committee (DMC).

Following this analysis, the DMC recommended the study should continue and enroll additional patients to the original target study population. Based on this recommendation, BMS will continue patient enrollment and advance the program as advised by the DMC, while remaining blinded to study data.

“BMS agrees with the decision made in consultation with the FDA and DMC to continue the phase 3 study and will move forward with recruiting additional patients,” said Laura Gault, MD, PhD, the senior vice president and head of neuroscience drug development at Bristol Myers Squibb. “Our decision to exclude patient data from sites where irregularities were observed reflects our unwavering commitment to safeguarding the integrity of our studies.”

The ADEPT-2 study is designed to evaluate the primary endpoint of changes in the Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions score and the key secondary endpoint of Clinical Global Impression-Severity, with additional assessments on safety and tolerability of Cobenfy compared with placebo. Participants aged 55 to 90 with possible or probable Alzheimer disease will be randomly assigned to either an oral capsule of Cobenfy or an oral capsule of placebo.²

Cobenfy, which is currently approved for the treatment of schizophrenia in adults, has the potential to be the first treatment in a new class of pharmacologic therapies targeting agitation and psychosis based on muscarinic receptor agonism. Additional trial results from the ADEPT program in psychosis associated with Alzheimer disease, including ADEPT-2, ADEPT-1 and ADEPT-4, are expected to read out by the end of 2026.

“Psychosis related to Alzheimer disease remains an area of tremendous unmet medical need, and maintaining rigorous standards is essential as we work to identify innovative treatment options for patients and families affected by this devastating condition,” concluded Gault.

References

1. Bristol Myers Squibb announces continuation of ADEPT-2 phase 3 study in psychosis associated with Alzheimer's disease. News release. December 3, 2025. Accessed December 3, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Continuation-of-ADEPT-2-Phase-3-Study-in-Psychosis-Associated-with-Alzheimers-Disease/default.aspx

2. Weiden PJ, Duerr HA. Cobenfy as an adjunctive agent in schizophrenia: Peter J. Weiden, MD, shares insights on the latest findings. Psychiatric Times. April 25, 2025. https://www.psychiatrictimes.com/view/cobenfy-as-an-adjunctive-agent-peter-weiden-md-latest-insights