A 52-week
open-label trial of antipsychotic Cobenfy (xanomeline-trospium chloride, X/T) found that patients with schizophrenia continued to show symptom improvement, with no new safety signals emerging, according to the results published in the
American Journal of Psychiatry.
Why It’s Relevant
Approved in September 2024,
Cobenfy is a novel antipsychotic that activates muscarinic acetylcholine receptors to regulate presynaptic synthesis of dopamine. The drug aims to address the cognitive and behavioral symptoms of schizophrenia while avoiding the side effects seen with current antipsychotics, such as movement disorders, weight gain, metabolic problems, and sedation.
Previous clinical trials found that participants given X/T had significantly greater reductions in overall symptoms after five weeks compared with those given placebo. However, as schizophrenia is a chronic disorder, long-term data are important to understand the full risk-benefit ratio of treatment.
By the Numbers
- EMERGENT-4 was an open label, 52-week extension trial involving 156 adults (ages 18 to 65) with schizophrenia who previously participated in one of the double-blind five-week studies. Participants received X/T up to a maximum dosage of twice-daily xanomeline 125mg/trospium 30mg.
- In total, 22% of participants completed the 52-week treatment.
- Participants’ average Positive and Negative Symptom Scale (PANSS) scores continued to improve through the open label period; at 52 weeks, average PANSS scores were 30 points lower than baseline. Similar patterns of continued improvement were observed for other clinical measures.
- About half (53%) of participants experienced at least one adverse event, with 11% withdrawing from the trial because of them. The most common side effects were gastrointestinal (nausea, vomiting, dyspepsia, dry mouth). X/T was not associated with extrapyramidal motor symptoms, hyperprolactinemia, somnolence or sedation, weight gain, or metabolic disorders.
What’s More
A second 52-week open-label trial is underway with a larger number of participants who have no prior X/T exposure and will provide additional information on the drug’s long-term safety and tolerability.
The Other Side
The researchers noted two important limitations: First, because this was a rollover trial, selection bias may have resulted from excluding participants who dropped out from the acute trials. Second, the proportion of participants who completed the open-label treatment period was low.
Takeaway Message
“The 52-week trial appears to confirm the favorable safety profile seen in the 5-week acute trials,” the researchers wrote. “In addition, X/T was associated with continued improvement over 52 weeks across all efficacy measures, suggesting that the beneficial effects of X/T do not appear to wear off.
Related Information
Source
Inder Kaul, et al. Long-term safety and efficacy of xanomeline and trospium chloride in schizophrenia: a 52-week open-label extension trial. American Journal of Psychiatry. Published February 4, 2026. doi: 10.1176/appi.ajp.2024118
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