In an unique interview with Psychiatric Occasions, Peter J. Weiden, MD, scientific professor of psychiatry at SUNY Stony Brook, supplied key scientific insights into the not too long ago launched research outcomes evaluating Cobenfy (xanomeline/trospium) as an adjunct remedy for schizophrenia.1,2
Accredited by the US Meals and Drug Administration (FDA) in 2024, Cobenfy represents the primary schizophrenia remedy to focus on muscarinic acetylcholine receptors relatively than dopamine pathways.3 “The FDA doesn’t name it an antipsychotic as a result of it’s not a dopamine medication,” mentioned Weiden. Its approval was primarily based on part 3 trial information displaying efficacy as monotherapy in grownup sufferers with schizophrenia, with impact sizes on par with established brokers corresponding to olanzapine and risperidone.
The current trial information, introduced through a Bristol Myers Squibb press launch,1 evaluated Cobenfy’s efficacy as an adjunctive remedy when there may be 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 had been stayed on their main antipsychotic and had 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 end result to a excessive placebo response, which regularly complicates the interpretation of adjunctive research. “These research are very arduous to do,” he added. “So the truth that it didn’t separate, at the least to me, just isn’t a shock… it is disappointing, but it surely occurs.” He additionally famous the press launch had restricted information, so it’s troublesome to make grand conclusions with out understanding extra.
From a regulatory perspective, Weiden mentioned until there are extra research or information, these findings make it unlikely that Cobenfy will obtain an expanded label for remedy resistance or adjunctive use right now. “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 scientific apply, the place antipsychotic mixture methods are frequent, albeit debated. “In my expertise, it is nearly like a faith—both you consider in it, or you do not,” he mentioned. “In case 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 protection findings had been reassuring. “Nothing bizarre occurred over the 6 weeks when sufferers had been mixed with Cobenfy and their present antipsychotic,” he reported.
Trying forward, Weiden emphasised that there’s nonetheless extra to study. “That is just the start of our understanding of the muscarinic system as a possible remedy strategy for sufferers with schizophrenia.”
Though the trial outcomes could not result in rapid regulatory adjustments, Weiden urged clinicians to remain engaged. “I feel it will be a vital research it doesn’t matter what,” he mentioned. “And there is nonetheless much more to be instructed.”
Dr Weiden is a scientific professor of psychiatry on the Renaissance College of Medication 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 at the moment on the audio system bureau for Bristol-Myers Squibb.
References
1. Bristol Myers Squibb publicizes topline outcomes from part 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-Section-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 Section 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