Cobenfy Phase III Results for Schizophrenia

In the Phase III trial, adjunctive Cobenfy treatment demonstrated a 2.0-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo with an atypical antipsychotic at Week 6, which did not reach the threshold for statistical significance for the primary endpoint (P = 0.11). Preliminary analyses suggest that Cobenfy as an adjunctive treatment to an atypical antipsychotic was associated with improvements in symptoms of schizophrenia compared to placebo plus an atypical antipsychotic for certain patients. In a post-hoc subgroup analysis there was a notable difference in response between subjects treated with risperidone as a background therapy compared with the remaining subjects treated with other background antipsychotics (non-risperidone). Cobenfy’s safety and tolerability profile as an adjunctive treatment was consistent with previous monotherapy trials.

Further analysis will follow, and the company will plan to speak with regulators about potential next steps.

"Adjunctive treatment trials in schizophrenia present significant clinical and methodological challenges," said Husseini Manji, MD, FRCPC, Co-Chair, UK Government Mental Health Goals Program and Professor, Department of Psychiatry, Oxford University. "When patients are already receiving treatment, demonstrating additional statistical benefit becomes inherently more difficult. However, it’s common for individuals to continue to experience persistent symptoms, and prescribers have adopted an approach to address this significant unmet need through adjunctive use. Although Cobenfy did not demonstrate a statistically significant improvement as an adjunctive treatment in this trial, the data are encouraging, showing a noteworthy improvement for the majority of patients in the trial, as well as a tolerable safety profile. These findings warrant additional follow up and may provide valuable direction in our ongoing search for complementary approaches to address these persistent treatment gaps."

"Historically, the development of an effective, adjunctive treatment for schizophrenia has been difficult due to inherent challenges like variable patient response, stringent trial design requirements, and the complexities of demonstrating incremental benefits beyond established antipsychotics," said Samit Hirawat, MD, executive vice president, chief medical officer and head of development at Bristol Myers Squibb. "Despite the complex and challenging nature of adjunctive studies, we wanted to pursue research in this area to help more patients struggling with this condition. While the primary endpoint in this trial did not meet statistical significance, we need to complete our analysis and will plan to engage with the medical community and regulators to discuss these results and potential next steps. Cobenfy monotherapy has shown positive efficacy and safety in four pivotal studies, and provides a meaningful, differentiated treatment for people living with schizophrenia.”

There is a robust clinical development program advancing for this important medicine across multiple neuropsychiatric conditions, including symptoms associated with Alzheimer's disease and autism spectrum disorder, bipolar disorder and other areas of significant clinical need.

Bristol Myers Squibb will complete a full evaluation of the Phase III trial data and intends to present detailed results at an upcoming medical conference.

About the Phase III ARISE Trial; The ARISE clinical trial (KAR-012) is a Phase III, 6-week, randomized, double-blind, placebo-controlled, multicenter, outpatient study evaluating Cobenfy (xanomeline and trospium chloride) as an adjunctive treatment in adults with schizophrenia who have inadequate response to their current antipsychotic treatment. The trial enrolled adults aged 18 to 65 years with schizophrenia who were on stable background therapy at the time of enrollment, with a Positive and Negative Syndrome Scale (PANSS) score of ≥70 at screening and randomization. The primary objective is to assess the efficacy of Cobenfy as an adjunctive treatment to one of several atypical antipsychotics compared to placebo with an atypical antipsychotic as measured by change from baseline in PANSS total score at Week 6. The study also evaluated several secondary endpoints, including changes in Personal Social Performance (PSP), Clinical Global Impression-Severity (CGI-S), PANSS Marder Positive and Negative symptom factor scores, categorical response (defined as the proportion of subjects achieving ≥30% improvement in PANSS total score at Week 6), and Preference of Medication (POM).

Following completion of the ARISE study, eligible participants may continue in a 52-week open-label extension (OLE) study to evaluate the long-term safety and tolerability of adjunctive Cobenfy treatment.