Cobenfy Falls Short of Statistical Significance as Additional Treatment for Schizophrenia in Phase III Clinical Trial

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Bristol Myers Squibb has shared results from its Phase III ARISE trial evaluating Cobenfy (xanomeline and trospium chloride) as an add on therapy to atypical antipsychotics in adults with inadequately controlled symptoms of schizophrenia. Despite demonstrating a 2.0-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score, the adjunctive treatment fell short of statistical significance for the primary endpoint.¹

In a press release, Husseini Manji, MD, FRCPC, co-chair, UK Government Mental Health Goals Program and professor, department of psychiatry, Oxford University, said: "Adjunctive treatment trials in schizophrenia present significant clinical and methodological challenges. 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."

According to preliminary analyses of the ARISE study, 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. Additional analyses showed a notable difference in response between subjects treated with risperidone as a background therapy compared with the remaining subjects treated with other background antipsychotics.

"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. 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,” added Samit Hirawat, MD, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, in the press release.

The 6-week, randomized, double-blind, placebo-controlled, multicenter, outpatient ARISE trial enrolled adults aged 18 to 65 years with schizophrenia who were on stable background therapy at the time of enrollment. In addition to the primary endpoint of change from baseline in PANSS total score at week 6, the trial evaluated multiple key secondary endpoints including changes in Personal Social Performance (PSP), Clinical Global Impression-Severity (CGI-S), and PANSS Marder Positive and Negative symptom factor scores.

Cobenfy was approved by the FDA for the treatment of schizophrenia in adults in September 2024. The approval was supported by data from the EMERGENT clinical program in which Cobenfy met its primary endpoint across the Phase III EMERGENT-2 and EMERGENT-3 studies. The therapy demonstrated a significant reduction in schizophrenia symptoms compared to placebo, as measured by the PANSS total score change.²

References

1. Bristol Myers Squibb Announces Topline Results from Phase 3 ARISE Trial Evaluating Cobenfy (xanomeline and trospium chloride) as an Adjunctive Treatment to Atypical Antipsychotics in Adults with Schizophrenia. News release. Bristol Myers Squibb. April 22, 2025. Accessed April 23, 2025. https://www.businesswire.com/news/home/20250422959331/en/Bristol-Myers-Squibb-Announces-Topline-Results-from-Phase-3-ARISE-Trial-Evaluating-Cobenfy-xanomeline-and-trospium-chloride-as-an-Adjunctive-Treatment-to-Atypical-Antipsychotics-in-Adults-with-Schizophrenia

2. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s COBENFY™ (xanomeline and trospium chloride), a First-In-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults. News release. Bristol Myers Squibb. September 26, 2024. Accessed April 23. 2025. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-COBENFY-xanomeline-and-trospium-chloride-a-First-In-Class-Muscarinic-Agonist-for-the-Treatment-of-Schizophrenia-in-Adults/default.aspx