Bristol Myers Squibb Advances ADEPT-2 Phase 3 Trial for Alzheimer’s-Related Psychosis Following Rigorous Data Review and FDA Alignment
Bristol Myers Squibb has announced a significant update regarding its ADEPT-2 Phase 3 clinical study, designed to evaluate the efficacy and safety of cobenfy in the treatment of psychosis associated with Alzheimer’s disease. In a move underscoring the company’s steadfast commitment to clinical trial integrity and patient safety, BMS will enroll additional patients into the study following a comprehensive internal review and consultation with regulatory authorities.
The decision to expand enrollment follows the identification of data irregularities linked to clinical trial execution at a limited number of study sites. Importantly, this assessment was conducted during a blinded review—meaning BMS remained unaware of treatment assignments or efficacy outcomes—prior to database lock. Upon discovering these execution-related inconsistencies, BMS proactively chose to exclude data from the affected sites from the primary efficacy and safety analysis. This action was taken not only to preserve the scientific rigor of the trial but also to uphold the highest ethical standards in clinical research.
In alignment with the U.S. Food and Drug Administration (FDA), BMS initiated an interim analysis of the remaining dataset. This analysis was carried out by an independent third party and subsequently reviewed by the study’s independent Data Monitoring Committee (DMC)—a group of external experts tasked with overseeing participant safety and trial conduct. Bristol Myers Following its evaluation, the DMC unanimously recommended continuing the ADEPT-2 study with the enrollment of additional patients to reach the originally intended target population size. BMS has accepted this recommendation and will proceed with recruitment accordingly, while remaining fully blinded to treatment-specific data throughout the process.
“Bristol Myers fully supports the joint decision—made in close consultation with the FDA and the DMC—to continue the Phase 3 study and to enroll additional patients,” said Dr. Laura Gault, MD, PhD, Senior Vice President and Head of Development for Neuroscience Drug Development at Bristol Myers Squibb. “Our choice to exclude data from sites where procedural irregularities were observed reflects our unwavering dedication to trial integrity. Psychosis related to Alzheimer’s disease represents a profound and persistent unmet medical need. For patients and their families, these symptoms can be among the most distressing aspects of the condition. Maintaining rigorous scientific and ethical standards is non-negotiable as we pursue innovative therapeutic options that could meaningfully improve lives.”
Cobenfy, BMS’s investigational agent, represents a potential first-in-class therapy for Alzheimer’s-related psychosis. Already approved for the treatment of schizophrenia in adults, cobenfy operates through a novel mechanism of action: selective muscarinic receptor agonism. Unlike traditional antipsychotics that primarily target dopamine pathways and carry significant safety concerns in elderly populations—especially those with dementia—cobenfy aims to modulate specific muscarinic receptors in the brain to address neuropsychiatric symptoms without the same risk profile. If successful, it could offer a much-needed, safer alternative for managing psychosis in Alzheimer’s patients, a population that currently has no FDA-approved pharmacologic treatments specifically for this indication.
The ADEPT clinical program is a robust, multi-study initiative evaluating cobenfy across various manifestations of Alzheimer’s disease–related behavioral symptoms. Beyond ADEPT-2, the program includes ADEPT-1 and ADEPT-4, each designed to assess different aspects of efficacy, safety, and dosing paradigms. BMS expects to report results from the full ADEPT program—including top-line data from all three trials—by the end of 2026. These readouts will be pivotal not only for regulatory submissions but also for informing clinical practice guidelines in geriatric psychiatry and neurology.
Bristol Myers Squibb’s broader strategy in Alzheimer’s disease reflects a dual-pronged approach: simultaneously pursuing disease-modifying therapies that target the underlying pathology of Alzheimer’s, while also developing symptomatic treatments like cobenfy that address the debilitating behavioral and psychological symptoms of dementia (BPSD). This comprehensive strategy acknowledges the multifaceted nature of the disease and the urgent need for solutions that improve both cognitive trajectory and quality of life for patients and caregivers alike.
The company’s emphasis on data integrity and regulatory collaboration in the ADEPT-2 trial also signals a larger industry trend toward greater transparency and accountability in late-stage clinical development—particularly in complex, high-stakes therapeutic areas like neurodegeneration. By acting swiftly to exclude compromised data and by engaging the FDA and an independent DMC early in the process, BMS has demonstrated a model of responsible drug development that prioritizes scientific validity over expediency.
As the ADEPT-2 trial moves forward with renewed enrollment, the neuroscience community—and millions of families affected by Alzheimer’s disease—will be watching closely. The successful development of a safe and effective treatment for Alzheimer’s-related psychosis would not only fill a critical therapeutic gap but also provide much-needed relief to caregivers often overwhelmed by the challenges of managing these distressing symptoms.
Bristol Myers Squibb remains committed to advancing the science of neurodegenerative disorders with rigor, compassion, and innovation. The continuation of the ADEPT-2 study is a testament to that mission—and a hopeful sign for the future of Alzheimer’s care.
About ADEPT-2
The ADEPT-2 study (clinicaltrials.gov, NCT06126224) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial assessing the safety and efficacy of Cobenfy in subjects with psychosis associated with Alzheimer’s disease dementia. The Bristol Myers study is designed to evaluate the primary endpoint of changes in the Neuropsychiatric Inventory-Clinician (NPI-C): Hallucinations and Delusions (H+D) score and the key secondary endpoint of Clinical Global Impression-Severity (CGI-S), with additional assessments on safety and tolerability of Cobenfy compared to placebo.
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