In an unique interview with Psychiatric Occasions, Peter J. Weiden, MD, medical professor of psychiatry at SUNY Stony Brook, provided key medical insights into the just lately launched research outcomes evaluating Cobenfy (xanomeline/trospium) as an adjunct remedy for schizophrenia.1,2
Authorized by the US Meals and Drug Administration (FDA) in 2024, Cobenfy represents the primary schizophrenia remedy to focus on muscarinic acetylcholine receptors somewhat than dopamine pathways.3 “The FDA doesn’t name it an antipsychotic as a result of it’s not a dopamine medication,” stated Weiden. Its approval was based mostly on section 3 trial knowledge exhibiting efficacy as monotherapy in grownup sufferers with schizophrenia, with impact sizes on par with established brokers corresponding to olanzapine and risperidone.
The latest trial knowledge, introduced through a Bristol Myers Squibb press launch,1 evaluated Cobenfy’s efficacy as an adjunctive remedy when there’s suboptimal response to a first-line antipsychotic. The outcomes didn’t meet the prespecified threshold for statistical significance.
“The outcomes didn’t meet statistical significance in sufferers who have been stayed on their major antipsychotic and have been randomized to Cobenfy versus placebo,” Weiden instructed Psychiatric Occasions. “Nevertheless, it was numerically higher than the placebo group.”
Weiden attributed a part of the result to a excessive placebo response, which regularly complicates the interpretation of adjunctive research. “These research are very onerous to do,” he added. “So the truth that it didn’t separate, a minimum of to me, just isn’t a shock… it is disappointing, however it occurs.” He additionally famous the press launch had restricted knowledge, so it’s tough to make grand conclusions with out realizing extra.
From a regulatory perspective, Weiden stated except there are extra research or knowledge, these findings make it unlikely that Cobenfy will obtain an expanded label for remedy resistance or adjunctive use presently. “This isn’t clozapine, and this has not helped us consider it as a form of clozapine.”
Nonetheless, the outcomes are removed from conclusive in medical apply, the place antipsychotic mixture methods are widespread, albeit debated. “In my expertise, it is nearly like a faith—both you consider in it, or you do not,” he stated. “In the event you’re a clinician who likes to mix antipsychotics for partial responders… the place would Cobenfy slot in that? There, the reply continues to be unclear.”
In excellent news, Weiden defined the security findings have been reassuring. “Nothing bizarre occurred over the 6 weeks when sufferers have been mixed with Cobenfy and their present antipsychotic,” he reported.
Wanting forward, Weiden emphasised that there’s nonetheless extra to study. “That is only the start of our understanding of the muscarinic system as a possible remedy strategy for sufferers with schizophrenia.”
Though the trial outcomes might not result in speedy regulatory modifications, Weiden urged clinicians to remain engaged. “I feel it is going to be a vital research it doesn’t matter what,” he stated. “And there is nonetheless much more to be instructed.”
Dr Weiden is a medical professor of psychiatry on the Renaissance Faculty of Drugs at Stony Brook College in New York. He’s Psychiatric Occasions’ Schizophrenia and Psychosis Part Editor.
Disclosure: Dr Weiden is a former worker of Karuna Therapeutics and is presently on the audio system bureau for Bristol-Myers Squibb.
References
1. Bristol Myers Squibb declares topline outcomes from section 3 ARISE trial evaluating Cobenfy (xanomeline and trospium chloride) as an adjunctive remedy to atypical antipsychotics in adults with schizophrenia. Information launch. April 22, 2025. Accessed April 25, 2025. https://information.bms.com/information/particulars/2025/Bristol-Myers-Squibb-Pronounces-Topline-Outcomes-from-Part-3-ARISE-Trial-Evaluating-Cobenfy-xanomeline-and-trospium-chloride-as-an-Adjunctive-Remedy-to-Atypical-Antipsychotics-in-Adults-with-Schizophrenia/default.aspx
2. Kuntz L. Cobenfy as Add-On Remedy for Schizophrenia Fails to Meet Major Endpoint in Part 3 ARISE Trial. Psychiatric Occasions. April 22, 2025. Accessed April 25, 2025. https://www.psychiatrictimes.com/view/cobenfy-as-add-on-treatment-for-schizophrenia-fails-to-meet-primary-endpoint-in-phase-3-arise-trial
3. Duerr HA. FDA Approves Cobenfy, A First In-Class Agent for Schizophrenia. Psychiatric Occasions. September 26, 2024. Accessed April 25, 2025. https://www.psychiatrictimes.com/view/fda-approves-cobenfy-for-schizophrenia
