Xanomeline/trospium chloride was approved for use by the U.S. Food and Drug Administration (with the brand name Cobenfy) in September 2024 for the treatment of schizophrenia in adults. Cognitive deficits are a stubborn feature in many cases of schizophrenia that significantly affect long-term trajectory and daily functioning.
“Collectively, the xanomeline/trospium clinical studies reflect the first time a monotherapy for the treatment of schizophrenia has shown a replicable cognitive benefit,” wrote lead author William Horan, Ph.D., executive director of clinical development at Bristol Myers, and colleagues. This study was sponsored by Karuna Therapeutics, a Bristol Myers Squibb company.
Across the two trials, 357 patients with acute schizophrenia were randomly assigned to receive oral xanomeline/trospium or placebo twice daily for five weeks. Most participants assigned to xanomeline/trospium were taking the maximum dosage of 125 mg/30 mg twice daily at week 5, with the remainder taking an intermediate dosage of 100 mg/20 mg.
Participants completed a computerized assessment of four key cognitive domains (executive function, visual memory, sustained attention, and verbal recall and recognition) at baseline, week 3, and week 5. Overall, 137 participants had significant cognitive deficits at baseline.
Among patients with cognitive impairment, those receiving xanomeline/trospium showed a significantly larger improvement in their cognitive scores from baseline to week 5 than the placebo group, with a calculated effect size of 0.54 (indicating a moderate level of improvement). The largest difference in performance between the xanomeline/trospium and placebo groups observed at week 5 was for verbal recall and recognition.
The effect remained significant after accounting for changes in positive and negative symptoms—suggesting that the effect on cognition is independent of improvement in psychotic symptoms. As with previous studies, there was no evidence of cognitive benefit for xanomeline/trospium when analyzing the full sample of 357 participants.
Cobenfy is the first drug approved for schizophrenia that does not act on dopamine (D2) receptors in the brain; rather it targets muscarinic acetylcholine receptors in areas of the brain more central to the cognitive and behavioral symptoms of schizophrenia.
For related information, see the Psychiatric News article “Questions and Excitement About New Schizophrenia Drug.”
(Image: Getty Images/iStock/BeritK)
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