BMS Schizophrenia Adjunct Therapy Cobenfy Phase III Trial Results Fail

On April 22, Bristol Myers Squibb (BMS) announced the topline results of the Phase 3 ARIS trial: the study evaluated Cobenfy (xanomeline/trospium chloride) as an adjunctive therapy to atypical antipsychotics in adults with schizophrenia who had inadequate symptom control.

However, the results showed that, compared to placebo with atypical antipsychotics, adjunctive treatment with Cobenfy did not meet the threshold for statistical significance on the primary endpoint of change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 6.

The ARISE clinical trial (KAR-012) was a 6-week, multicenter, Phase 3 randomized, double-blind, placebo-controlled study assessing the efficacy and safety of Cobenfy (xanomeline and trospium chloride) as adjunctive treatment for adults with inadequately controlled schizophrenia symptoms. In the Phase 3 trial, adjunctive Cobenfy reduced the PANSS total score by 2.0 points at week 6 compared to placebo with atypical antipsychotics, which did not meet the statistical significance threshold for the primary endpoint (P = 0.11).

Subgroup and Exploratory Analyses

Although the primary endpoint was not met, numerical trends suggested some symptom improvement with Cobenfy adjunctive therapy. A post-hoc subgroup analysis indicated that patients receiving risperidone as their background antipsychotic demonstrated a statistically significant greater PANSS reduction (p = 0.03), whereas the subgroup on olanzapine did not show a similar effect.

Safety

The safety profile of Cobenfy as an adjunctive treatment was consistent with previous monotherapy studies, and no new safety signals were observed.

“Adjunctive therapy trials in schizophrenia face significant clinical and methodological challenges,” said Dr. Husseini Manji, Professor of Psychiatry at the University of Oxford. “Despite not reaching statistical significance in this study, the data remain encouraging—particularly the trends in symptom improvement for many patients and the favorable safety profile—warranting further investigation.”

“Developing adjunctive treatments has historically been difficult, but Cobenfy monotherapy has demonstrated efficacy in four key trials,” said Dr. Samit Hirawat, Chief Medical Officer at BMS. “We will discuss these results with regulatory authorities and the medical community to define the next steps.”

Next Steps

BMS will continue to analyze the ARISE data in depth and plans to present full results at upcoming medical conferences. The clinical development program for Cobenfy remains ongoing, with additional studies in Alzheimer’s disease, autism spectrum disorder, bipolar disorder, and other neuropsychiatric conditions.